Materiały źródłowe

• #1 Signaling pathways in obesity: mechanisms and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01149-x

  Obesity is a complex, chronic disease and global public health challenge. Characterized by excessive fat accumulation in the body, obesity sharply increases the risk of several diseases, such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and is linked to lower life expectancy. […] Over the past decades, the pathophysiology of obesity has been extensively investigated, and an increasing number of signal transduction pathways have been implicated in obesity, making it possible to fight obesity in a more effective and precise way. […] In this review, we summarize recent advances in the pathogenesis of obesity from both experimental and clinical studies, focusing on signaling pathways and their roles in the regulation of food intake, glucose homeostasis, adipogenesis, thermogenesis, and chronic inflammation.

• #2

  https://www.archivesofmedicalscience.com/Obesity-and-inflammation-the-linking-mechanism-and-the-complications,61147,0,2.html

  Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. […] The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. […] It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.

• #3 Obesity Pathogenesis: An Endocrine Society Scientific Statement

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5546881/

  Obesity is among the most common and costly chronic disorders worldwide. […] A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. […] Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. […] The ongoing study of how genetic, developmental, and environmental forces affect the energy homeostasis system will help us better understand these mechanisms and are therefore a major focus of this statement. […] Obesity pathogenesis involves two related but distinct processes: (1) sustained positive energy balance (energy intake energy expenditure) and (2) resetting of the body weight set point at an increased value.

• #4 Obesity Pathogenesis: An Endocrine Society Scientific Statement | MedPage Today

  https://www.medpagetoday.com/clinical-connection/cardio-endo/78277

  Obesity is among the most common and costly chronic disorders worldwide. […] A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. […] Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. […] The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences. […] Obesity pathogenesis involves two related but distinct processes: (1) sustained positive energy balance (energy intake > energy expenditure) and (2) resetting of the body weight „set point” at an increased value.

• #5 Obesity Pathogenesis: An Endocrine Society Scientific Statement

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5546881/

  How the increased body weight comes to be biologically defended remains uncertain, although ongoing research is beginning to shed some light on underlying mechanisms. […] Studies investigating the adaptive responses of normal-weight humans and animals to changes in body weight support the concept of a physiologically important energy homeostasis system. […] These adaptive responses to weight loss are reported in both individuals who are obese and lean individuals, therefore suggesting that obesity pathogenesis involves the physiological defense of a higher level of body fat. […] This observation suggests that dysfunction of the energy homeostasis system is both necessary and sufficient for the biological defense of elevated body weight in individuals who are obese. […] What remains unclear is how this dysfunction is linked to factors that enable excess weight gain, such that excess body-fat mass comes to be biologically defended.

• #6 On the pathogenesis of obesity: causal models and missing pieces of the puzzle | Nature Metabolism

  https://www.nature.com/articles/s42255-024-01106-8

  The workshop did not aspire to reach consensus on what causes obesity, but rather the intent was to operationally define commonly used terms, delineate the structure of each model and overlay suggested routes and causal pathways on top of a common physiological background of energy metabolism and body weight regulation, discuss the importance of purported causal factors for weight gain, brainstorm on the key scientific questions that need to be answered and outline the general principles of appropriate experiments to test between the relevant hypotheses. […] According to the EBM, the changing food environment caused increased obesity prevalence primarily by increasing food intake above requirements (positive energy balance), resulting in excess accumulation of body fat. […] According to the CIM, the primary cause of increased obesity prevalence is an alteration in fuel partitioning that favours channelling of ingested energy-yielding substrates away from pathways of oxidation toward storage in adipose and perhaps other tissues. This metabolic shift is perceived by the brain as a state of lack of energy, leading to decreased energy expenditure or increased food intake to compensate, eventually resulting in obesity.

• #7 Obesity Pathogenesis: An Endocrine Society Scientific Statement

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5546881/

  The adipocyte hormone leptin, which circulates at concentrations proportional to body-fat mass, plays a significant role in the relationship between obesity and energy homeostasis. […] However, these observations do not indicate that genetic deficiencies of leptin or its cognate receptor are important causes of human obesity. […] Given the evolutionary considerations alluded to above, the primary role played by leptin-responsive neurocircuits may be related more to preventing loss of body fat than to defending against its increase. […] The hypothesis that leptin plays a direct role in these processes is supported by evidence of its direct effects on lipid partitioning in skeletal muscle. […] Although it is possible that variations in body composition among individuals of the same body weight reflect (to some extent) the consequences of such processes, achieving clinical obesity in this manner must be rare, because most individuals who are obese have absolute increases of both lean and fat mass.

• #8 Broken Energy Homeostasis and Obesity Pathogenesis: The Surrounding Concepts

  https://www.mdpi.com/2077-0383/7/11/453

  Once the energy homeostatic balance is „broken”, the neuro-endocrine system will fail to establish energy balance due to the inefficiency of this system. […] The starting point of metabolic consequences of obesity is mainly due to increased fat storage with the visceral adiposity as the most deleterious form. […] These selected examples highlight some of the effects of obesity on key metabolic tissues (adipose tissue, liver and muscle), placing obesity among the top metabolic disorders and further support the need for a „metabolic classification” for obesity. […] Within this context, it would seem acceptable to assume that sleep shortage and psychological factors contribute to the status of a „broken homeostatic system” described previously, leading to inefficient energy metabolism control. […] Such an approach could be a starting point towards a more sophisticated neuropharmacological treatment of obesity that targets the neurological structures and neurotransmitters involved in energy homeostasis control.

• #9 Obesity Pathogenesis: An Endocrine Society Scientific Statement

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5546881/

  Collectively, these data suggest that diet composition per se contributes far less to the etiology of obesity than do contributions made by the net imbalance of intake and expenditure. […] The identification of neuromolecular mechanisms that integrate short-term and long-term control of feeding behavior, such that calorie intake precisely matches energy expenditure over long time intervals, will almost certainly enable better preventive and therapeutic approaches to obesity.

• #10 Pathophysiology of Obesity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572076/

  Obesity is a chronic disease having a major public health concern. Obesity is a mild state of chronic inflammation of adipose tissue and a state of malnutrition by excess, which leads to a defective hormonal and immune system. This activity reviews the pathophysiology of obesity, inflammatory markers secreted by excessive fat deposition in adipose tissue, and their effects on chronic diseases such as hypertension, diabetes, and dyslipidemia. […] Obesity has inflammatory components, directly and indirectly, related to major chronic diseases such as diabetes, atherosclerosis, hypertension, and several types of cancer. Overweight and obese individuals have altered circulatory levels of inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-, C-reactive protein (CRP), IL-18, resistin, and visfatin.

• #11 Pathophysiology of Obesity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572076/

  Obesity is also referred to as chronic-low-grade inflammation or metabolic inflammation, which is often the focus in the pathogenesis of several diseases such as coronary artery disease, atherosclerosis, and insulin resistance. Adipose tissue is classified as a complex secretory organ that plays many roles in metabolism. This can modulate energy expenditure, appetite, insulin sensitivity, bone metabolism, reproductive and endocrine functions, inflammation, and immunity and act as a triacylglycerol reservoir. […] The role of increased pro-inflammatory cytokine secretion in obese patients is currently unknown. It is speculated that the answer to this question is correlated with the enlarged, lipid-rich adipocytes seen in obese individuals. […] Several studies suggest adipose tissue can collectively secrete more than 50 hormones and signaling molecules termed adipokines. These adipokines play a vital role in immunity and glucose metabolism. […] The mechanisms between obesity and chronic inflammation are not completely understood, but different likely explanations have been proposed.

• #12

  https://www.archivesofmedicalscience.com/Obesity-and-inflammation-the-linking-mechanism-and-the-complications,61147,0,2.html

  Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. […] The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. […] It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.

• #13 Signaling pathways in obesity: mechanisms and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01149-x

  Although the underpinnings of its pathogenesis are not yet fully understood yet, obesity is well recognized as a heterogeneous disorder regulated by multiple pathways. […] The evolving understanding of the signaling pathways involved in obesity occurrence and development allows us to fight obesity in a more precise way. […] MAPK signaling members, including extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38 MAPK, play a pivotal role in the regulation of appetite, adipogenesis, glucose homeostasis, and thermogenesis. […] The MAPK signaling pathway is closely involved in the development of insulin resistance. […] The PI3K/AKT pathway regulates appetite via the CNS and peripheral tissues. […] The JAK/STAT signaling pathway is correlated with the melanocortin pathway since the energy homeostasis regulated by leptin is mediated by JAK/STAT.

• #14 Signaling pathways in obesity: mechanisms and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01149-x

  Although the underpinnings of its pathogenesis are not yet fully understood yet, obesity is well recognized as a heterogeneous disorder regulated by multiple pathways. […] The evolving understanding of the signaling pathways involved in obesity occurrence and development allows us to fight obesity in a more precise way. […] MAPK signaling members, including extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38 MAPK, play a pivotal role in the regulation of appetite, adipogenesis, glucose homeostasis, and thermogenesis. […] The MAPK signaling pathway is closely involved in the development of insulin resistance. […] The PI3K/AKT pathway regulates appetite via the CNS and peripheral tissues. […] The JAK/STAT signaling pathway is correlated with the melanocortin pathway since the energy homeostasis regulated by leptin is mediated by JAK/STAT.

• #15 Signaling pathways in obesity: mechanisms and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01149-x

  The TGF- superfamily consists of TGF-1-3, activins/inhibins, growth differentiation factors (GDFs), myostatin, and BMPs, playing diverse roles in appetite regulation, lipid metabolism, and glucose homeostasis. […] AMPK functions as a fuel gauge to monitor cellular energy status and is highly conserved across all eukaryotic species. […] The Wnt/-catenin pathway has been suggested to have a negative effect on adipogenesis and obesity. […] The activation/inhibition of the Wnt signaling pathway leads to different effects in obesity pathogenesis, which is determined by the specific pathways of action. […] ER stress refers to a condition in which unfolded or misfolded proteins accumulate in ER and leads to stress conditions. […] A plethora of evidence from animal and clinical studies shows that elevated ER stress in adipose tissue is induced by obesity, which in turn impairs ER functions and leads to metabolic dysfunction within the cell.

• #16 Effect of hypoglycemic agents with weight loss effect plus a high protein diet and moderate exercise on diabetes remission in adults with obesity and type 2 diabetes: a randomized controlled trial | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04072-4

  The prevalence of obesity is increasing drastically in China in the past decades due to westernized dietary patterns and lack of physical activity. Obesity can cause insulin resistance (IR) and the development of type 2 diabetes (T2D) through a variety of biological pathways. […] IR plays a crucial role in the pathogenesis of T2D and other cardiometabolic diseases. Systemic IR, attributed to excessive accumulation of adipose tissue in liver and skeletal muscle, causes a variety of cardiometabolic diseases and is generally assessed by HOMA-IR in clinical practice. […] Significant improvements of HOMA-IR, HOMA-AD and Adipo-IR after weight loss might be the potential pathophysiological mechanisms of diabetes remission. […] The beneficial improvements in IR, inflammation marker, adipocytokine, myokine and hepatokine, might be crucial pathophysiological changes involved in weight loss and diabetes remission.

• #17 Mechanism linking diabetes mellitus and obesity | DMSO

  https://www.dovepress.com/mechanism-linking-diabetes-mellitus-and-obesity-peer-reviewed-fulltext-article-DMSO

  Body mass index has a strong relationship to diabetes and insulin resistance. In obese individuals, the amount of nonesterified fatty acids, glycerol, hormones, cytokines, proinflammatory markers, and other substances that are involved in the development of insulin resistance, is increased. […] Insulin resistance with impairment of -cell function leads to the development of diabetes. Gaining weight in early life is associated with the development of type 1 diabetes. NEFA is a cornerstone in the development of insulin resistance and in the impairment of -cell function. […] The cornerstone factor affecting insulin insensitivity is the release of NEFAs. Increased release of NEFAs is observed in type 2 diabetes and in obesity, and it is associated with insulin resistance in both conditions.

• #18 Mechanism linking diabetes mellitus and obesity | DMSO

  https://www.dovepress.com/mechanism-linking-diabetes-mellitus-and-obesity-peer-reviewed-fulltext-article-DMSO

  Body mass index has a strong relationship to diabetes and insulin resistance. In obese individuals, the amount of nonesterified fatty acids, glycerol, hormones, cytokines, proinflammatory markers, and other substances that are involved in the development of insulin resistance, is increased. […] Insulin resistance with impairment of -cell function leads to the development of diabetes. Gaining weight in early life is associated with the development of type 1 diabetes. NEFA is a cornerstone in the development of insulin resistance and in the impairment of -cell function. […] The cornerstone factor affecting insulin insensitivity is the release of NEFAs. Increased release of NEFAs is observed in type 2 diabetes and in obesity, and it is associated with insulin resistance in both conditions.

• #19 Mechanism linking diabetes mellitus and obesity | DMSO

  https://www.dovepress.com/mechanism-linking-diabetes-mellitus-and-obesity-peer-reviewed-fulltext-article-DMSO

  A second factor that might contribute to a continuous loss of function of -cells is increasing plasma NEFA levels. Despite the fact that NEFAs play a major role in insulin release, the continuous exposure to NEFAs is related to significant malfunction in glucose-stimulated insulin secretion pathways and reduced insulin biosynthesis. […] The two actions of NEFA contribute to a significant etiology that links -cell dysfunction and insulin resistance in people with type 2 diabetes, and those who are at risk for the disease.

• #20 Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora

  https://www.mdpi.com/2227-9059/12/8/1633

  Furthermore, more and more studies have confirmed that there is a strong relationship between obesity and intestinal flora. […] The intestinal microbiota can not only mediate obesity by regulating human energy metabolism, triggering chronic inflammation and affecting intestinal hormone secretion, but also actively participate in the metabolism of bile acids, short-chain fatty acids (SCAFs), and carbohydrates, eventually leading to obesity. […] The interaction between intestinal flora and DNA methylation is essential in the regulation and development of obesity, highlighting the interconnectedness of these factors. […] Therefore, investigating the interaction between DNA methylation and intestinal flora composition in obesity could offer innovative therapeutic strategies for prevention and management.

• #21 Nutritional and Biochemical Aspects of Obesity: A Comprehensive Study to Understand Obesity Mechanism

  https://www.jmchemsci.com/article_211189.html

  Obesity was found to disrupt the intestinal microbiota, further exacerbating conditions like dyslipidemia, hypertension, and liver diseases. […] Moreover, the association between obesity and cancer development is linked to hormonal and immune system changes driven by adipose tissue. […] Obesity is a complex condition involving multifaceted interactions between various adipose tissues, metabolic processes, and the intestinal microbiota. […] A better understanding of these interactions offers crucial insights into the mechanisms driving obesity-related comorbidities. […] Targeting adipose tissue biology and restoring metabolic balance may present promising strategies for preventing and managing obesity and its associated diseases.

• #22 Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora

  https://www.mdpi.com/2227-9059/12/8/1633

  Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. […] Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. […] DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. […] The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. […] Research has revealed that alterations in DNA methylation patterns, induced by high-calorie diets and sedentary lifestyles, can affect the expression of genes involved in energy metabolism and fat storage, ultimately promoting the onset of obesity.

• #23 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20240131/Study-reveals-key-mechanism-behind-obesity-related-metabolic-dysfunction.aspx

  Obesity has become a global epidemic, increasing the incidence of non-alcoholic steatohepatitis, diabetes, and other cardiometabolic disorders. […] Obese individuals have impaired mitochondrial function, and the underlying mechanisms and their contribution to obesity remain unclear. […] In the present study, researchers demonstrated increased expression and activity of Ras-like proto-oncogene A (RalA) in adipocytes from obese mice and attenuation of HFD-induced obesity upon targeted Rala deletion in white adipocytes. […] RalA depletion reduced insulin-stimulated glucose uptake in BAT and iWAT. […] HFD-fed RalaAKO mice also showed improved glucose tolerance, without changes in insulin tolerance; they also had reduced insulin levels and improved homeostasis model assessment of insulin resistance (HOMA-IR) than controls. […] Overall, chronically increased RalA activity plays a role in repressing energy expenditure in obese adipose tissue by shifting mitochondrial dynamics towards excessive fission and contributing to weight gain and metabolic dysfunction.

• #24 Researchers Identify Mechanism That May Drive Obesity Epidemic | NYU Langone News

  https://nyulangone.org/news/reSearchers-identify-mechanism-may-drive-obesity-epidemic

  A molecular trick that kept our ancient ancestors from starving may now be contributing to the obesity epidemic, a new study finds. […] We discovered an anti-starvation mechanism that has become a curse in times of plenty because it sees cellular stress created by overeating as similar to stress created by starvation and puts the brakes on our ability to burn fat, says lead study author Ann Marie Schmidt, MD, the Dr. Iven Young Professor of Endocrinology at NYU School of Medicine. […] Published online July 16 in Cell Reports, the current study reveals that the natural function of a protein on the surface of fat cells, called RAGE, is to stop the breakdown of stored fat in the face of stress. […] A disturbing possibility, says Dr. Schmidt, is that many proteins and fats have come to activate the RAGE brake as they warp and stack up, as toxic oligomers, in people who eat more than their ancestors did.

• #25 Researchers Identify Mechanism That May Drive Obesity Epidemic | NYU Langone News

  https://nyulangone.org/news/reSearchers-identify-mechanism-may-drive-obesity-epidemic

  The current study found that removing RAGE from fat cells caused mice to gain up to 75 percent less weight during 3 months of high-fat feeding, despite equal amounts of food consumption and physical activity, than mice with the RAGE brake on. […] In both sets of experiments, the deletion of RAGE from fat cells released the braking mechanisms that restrained energy expenditure. […] Importantly, RAGE is much more active during metabolic stress, such as starving or overeating, than in everyday function, which suggests it can be safely interfered with through drugs, the authors say. […] Because RAGE evolved out of the immune system, blocking it may also reduce the inflammatory signals that contribute to insulin resistance driving diabetes, says Dr. Schmidt.

• #26 CNIC identifies key mechanism in fat cells to combat obesity

  https://www.drugtargetreview.com/news/154431/cnic-identifies-key-mechanism-in-fat-cells-to-combat-obesity/

  CNIC researchers have identified a mechanism in fat cells that helps them safely store excess fat, offering new insights for combating obesity and related metabolic diseases. […] This breakthrough, published in Nature Communications, opens the door to new therapeutic strategies for treating obesity, lipodystrophy, metabolic syndrome, and other diseases linked to fat accumulation. […] The CNIC team set out to understand how adipocytes adapt to mechanical stress as they expand to store excess fat. […] This process protects the adipocytes from rupture and prevents the inflammatory responses associated with fat cell damage. […] However, caveolae do more than provide structural support, they also play a critical role in regulating metabolism. […] This dysfunction is linked to conditions such as lipodystrophy, where the body cannot store fat properly, resulting in severe metabolic disturbances. […] These results give us a better understanding of how adipose tissue responds to the mechanical forces associated with energetic excess. […] The study represents a major step forward in understanding how fat cells protect the body from the harmful effects of excessive fat storage.

• #27 Obesity and hormones | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones

  The hormones leptin, insulin, oestrogens, androgens and growth hormone influence our appetite, metabolism and body fat distribution. […] People who are obese have hormone levels that encourage the accumulation of body fat. […] Hormones are chemical messengers that regulate processes in our body. They are one factor in causing obesity. The hormones leptin and insulin, sex hormones and growth hormone influence our appetite, metabolism (the rate at which our body burns kilojoules for energy), and body fat distribution. People who are obese have levels of these hormones that encourage abnormal metabolism and the accumulation of body fat. […] Insulin, a hormone produced by the pancreas, is important for the regulation of carbohydrates and the metabolism of fat. Insulin stimulates glucose (sugar) uptake from the blood in tissues such as muscles, the liver and fat. This is an important process to make sure that energy is available for everyday functioning and to maintain normal levels of circulating glucose. In a person who is obese, insulin signals are sometimes lost and tissues are no longer able to control glucose levels. This can lead to the development of type II diabetes and metabolic syndrome.

• #28 Obesity and hormones | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones

  The hormones leptin, insulin, oestrogens, androgens and growth hormone influence our appetite, metabolism and body fat distribution. […] People who are obese have hormone levels that encourage the accumulation of body fat. […] Hormones are chemical messengers that regulate processes in our body. They are one factor in causing obesity. The hormones leptin and insulin, sex hormones and growth hormone influence our appetite, metabolism (the rate at which our body burns kilojoules for energy), and body fat distribution. People who are obese have levels of these hormones that encourage abnormal metabolism and the accumulation of body fat. […] Insulin, a hormone produced by the pancreas, is important for the regulation of carbohydrates and the metabolism of fat. Insulin stimulates glucose (sugar) uptake from the blood in tissues such as muscles, the liver and fat. This is an important process to make sure that energy is available for everyday functioning and to maintain normal levels of circulating glucose. In a person who is obese, insulin signals are sometimes lost and tissues are no longer able to control glucose levels. This can lead to the development of type II diabetes and metabolic syndrome.

• #29 Obesity and hormones | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones

  Body fat distribution plays an important role in the development of obesity-related conditions such as heart disease, stroke and some forms of arthritis. […] The pituitary gland in our brain produces growth hormone, which influences a person’s height and helps build bone and muscle. Growth hormone also affects metabolism (the rate at which we burn kilojoules for energy). Researchers have found that growth hormone levels in people who are obese are lower than in people of normal weight. […] Obesity is also associated with low-grade chronic inflammation within the fat tissue. Excessive fat storage leads to stress reactions within fat cells, which in turn lead to the release of pro-inflammatory factors from the fat cells themselves and immune cells within the adipose (fat) tissue. […] Obesity is associated with an increased risk of a number of diseases, including cardiovascular disease, stroke and several types of cancer, and with decreased longevity (shorter life span) and lower quality of life. […] Studies have also shown that weight loss as a result of healthy diet and exercise or bariatric surgery leads to improved insulin resistance, decreased inflammation and beneficial modulation of obesity hormones.

• #30 GLP-1 Agonists: What They Are, How They Work & Side Effects

  https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists

  GLP-1 agonists are a class of medications that mainly help manage blood sugar (glucose) levels in people with Type 2 diabetes. Some GLP-1 agonists can also help treat obesity. […] The FDA currently approves the use of semaglutide and high-dose liraglutide to help treat obesity. This is because these GLP-1 agonists have weight loss effects. Obesity is a chronic condition in which you have a body mass index (BMI) of 30 or higher. […] The satiety effect of GLP1-agonists reduces your food intake, appetite and hunger. These combined effects often result in weight loss.

• #31 Zepbound for Weight Loss: Uses, Dosage, Side Effects – Drugs.com

  https://www.drugs.com/zepbound.html

  Zepbound (tirzepatide) is an FDA-approved medicine used for weight loss and weight management to help you lose weight and keep weight off, and it is also used for obstructive sleep apnea (OSA) with obesity. […] Zepbound works by reducing your appetite and making you feel full more quickly and for a longer period of time, so you eat less and lose weight. […] Zepbound works like two natural hormones in our bodies, called GIP and GLP-1, which help control appetite, blood sugar levels, and digestion. When Zepbound binds to GIP and GLP-1 receptors, it slows the rate food passes through your body, making you feel full longer, and the pancreas releases more insulin, lowering the amount of sugar your liver makes. This helps helps weight loss and may also lower blood sugar levels. Zepbound is a GIP and GLP-1 receptor agonist. Zepbound’s mechanism of action is by activating both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) hormone receptors. […] In studies with rats, tirzepatide, and medicines that work in the same way caused thyroid tumors, including thyroid cancer. It is not known whether Zepbound will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.

• #32 NodThera’s Oral NLRP3 Inhibitor NT-0796 Enhances and Sustains Weight Loss in Combination with GLP-1 – Nodthera

  https://www.nodthera.com/news/nodtheras-oral-nlrp3-inhibitor-nt-0796-enhances-and-sustains-weight-loss-in-combination-with-glp-1/

  Data published in Obesity journal show enhanced weight loss effect of NT-0796 when combined with semaglutide in preclinical obesity model. […] Obese state completely reversed with 30% weight loss and reversal of hypothalamic inflammation. […] NT-0796 uniquely positioned as an oral, well tolerated therapeutic to induce healthier and sustained weight loss, both as a monotherapy and in combination with GLP-1RAs. […] These new data build on NodTheras earlier preclinical and clinical work and support the potential of central NLRP3 inhibition to reset multiple dysregulated cardiometabolic pathways, restoring the bodys natural metabolic balance and enabling sustained and healthy weight loss. […] This supports a model consistent with the observed reduction in both peripheral and hypothalamic (brain) inflammation as a druggable mechanism in obesity pathogenesis.

• #33 NodThera’s Oral NLRP3 Inhibitor NT-0796 Enhances and Sustains Weight Loss in Combination with GLP-1 – Nodthera

  https://www.nodthera.com/news/nodtheras-oral-nlrp3-inhibitor-nt-0796-enhances-and-sustains-weight-loss-in-combination-with-glp-1/

  By harnessing both peripheral and central NLRP3 inhibition to correct multiple dysregulated pathways in the brain and throughout the body we have the potential to bring profound cardiometabolic benefits to patients, establishing an enhanced treatment approach to weight management that would enable sustained and healthier weight loss.

• #34 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology involves the complex interplay of genetic, environmental, and metabolic factors affecting energy balance and fat storage in the body. Dysregulation in hormones like leptin and insulin, along with inflammation, contributes to abnormal fat accumulation and chronic weight gain. Understanding obesity’s underlying mechanisms is crucial for developing effective obesity management and prevention strategies. […] Obesity is characterized by an imbalance between energy intake and energy expenditure. Various mechanisms contribute to this imbalance, including genetic, environmental, and psychological factors, leading to an increased body mass index (BMI). Key mechanisms include: Hypothalamic regulation: The hypothalamus plays a crucial role in managing hunger and energy balance. Dysfunctions in this area can lead to overeating and weight gain. Genetic predisposition: Some individuals have a genetic tendency to accumulate fat due to hereditary traits. Energy homeostasis: A disruption in the balance of energy consumed through food and energy expended through physical activity leads to obesity. Lipid metabolism disruption: Excessive fat storage in adipose tissue contributes to obesity, affecting how the body processes lipids.

• #35 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology involves the complex interplay of genetic, environmental, and metabolic factors affecting energy balance and fat storage in the body. Dysregulation in hormones like leptin and insulin, along with inflammation, contributes to abnormal fat accumulation and chronic weight gain. Understanding obesity’s underlying mechanisms is crucial for developing effective obesity management and prevention strategies. […] Obesity is characterized by an imbalance between energy intake and energy expenditure. Various mechanisms contribute to this imbalance, including genetic, environmental, and psychological factors, leading to an increased body mass index (BMI). Key mechanisms include: Hypothalamic regulation: The hypothalamus plays a crucial role in managing hunger and energy balance. Dysfunctions in this area can lead to overeating and weight gain. Genetic predisposition: Some individuals have a genetic tendency to accumulate fat due to hereditary traits. Energy homeostasis: A disruption in the balance of energy consumed through food and energy expended through physical activity leads to obesity. Lipid metabolism disruption: Excessive fat storage in adipose tissue contributes to obesity, affecting how the body processes lipids.

• #36 Mechanism of Acupuncture in Treating Obesity: Advances and Prospects | The American Journal of Chinese Medicine

  https://worldscientific.com/doi/10.1142/S0192415X24500010?srsltid=AfmBOoqIKYDq_PEhe3dw0m2QvMl_4gS8OKG5PV1nbhMFNvBrzIjMI878

  The hypothalamus is the center of food intake and energy metabolism in the CNS, and it affects feeding by integrating neural signals that come from the brainstem or even higher cortical centers and peripheral humoral signals that influence energy expenditure and food intake, ultimately achieving the goal of weight control. […] Acupuncture can reduce weight by inhibiting the expressions of AgRP and NPY and improve insulin resistance (IR). […] The POMC and CART neurons work together to control appetite. […] Acupuncture can reduce the excitability of the LHA, inhibit hyperphagia, and regulate the activity of 5-HT, the catecholamine neurotransmitter, and ATPase activity in the LHA, eventually leading to weight loss. […] Acupuncture shows a better effect in promoting insulin sensitivity through attenuating inflammation in obese patients.

• #37 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology involves the complex interplay of genetic, environmental, and metabolic factors affecting energy balance and fat storage in the body. Dysregulation in hormones like leptin and insulin, along with inflammation, contributes to abnormal fat accumulation and chronic weight gain. Understanding obesity’s underlying mechanisms is crucial for developing effective obesity management and prevention strategies. […] Obesity is characterized by an imbalance between energy intake and energy expenditure. Various mechanisms contribute to this imbalance, including genetic, environmental, and psychological factors, leading to an increased body mass index (BMI). Key mechanisms include: Hypothalamic regulation: The hypothalamus plays a crucial role in managing hunger and energy balance. Dysfunctions in this area can lead to overeating and weight gain. Genetic predisposition: Some individuals have a genetic tendency to accumulate fat due to hereditary traits. Energy homeostasis: A disruption in the balance of energy consumed through food and energy expended through physical activity leads to obesity. Lipid metabolism disruption: Excessive fat storage in adipose tissue contributes to obesity, affecting how the body processes lipids.

• #38 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology refers to the underlying mechanisms and factors leading to excessive fat accumulation in the body, impacting health and well-being. […] Recent advances in genetic research have identified specific gene mutations that could significantly impact the energy balance and appetite regulation in individuals with morbid obesity. Variations in these genes may lead to increased fat storage and difficulty in losing weight, highlighting potential targets for personalized treatments in severe obesity cases. […] The pathophysiological changes in morbid obesity result in numerous detrimental health impacts. These include: Cardiovascular diseases: The risk is substantially higher due to factors like hypertension and dyslipidemia. Type 2 diabetes: Enhanced insulin resistance directly links morbid obesity to a higher prevalence of diabetes. Sleep apnea: Excessive weight increases breathing difficulties during sleep. Osteoarthritis: The added weight places stress on joints, exacerbating wear and tear. Psychological effects: Including depression and decreased quality of life due to social and physical limitations.

• #39 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology involves the complex interplay of genetic, environmental, and metabolic factors affecting energy balance and fat storage in the body. Dysregulation in hormones like leptin and insulin, along with inflammation, contributes to abnormal fat accumulation and chronic weight gain. Understanding obesity’s underlying mechanisms is crucial for developing effective obesity management and prevention strategies. […] Obesity is characterized by an imbalance between energy intake and energy expenditure. Various mechanisms contribute to this imbalance, including genetic, environmental, and psychological factors, leading to an increased body mass index (BMI). Key mechanisms include: Hypothalamic regulation: The hypothalamus plays a crucial role in managing hunger and energy balance. Dysfunctions in this area can lead to overeating and weight gain. Genetic predisposition: Some individuals have a genetic tendency to accumulate fat due to hereditary traits. Energy homeostasis: A disruption in the balance of energy consumed through food and energy expended through physical activity leads to obesity. Lipid metabolism disruption: Excessive fat storage in adipose tissue contributes to obesity, affecting how the body processes lipids.

• #40 Obesity: Etiologic and pathophysiological analysis | Endocrinología y Nutrición (English Edition)

  https://www.elsevier.es/en-revista-endocrinologia-nutricion-412-articulo-obesity-etiologic-pathophysiological-analysis-S2173509313000081

  However, imbalances in the composition of the intestinal microbiota have been associated with the occurrence of insulin resistance and body weight increase. […] According to the first law of thermodynamics, obesity is the result of an imbalance between energy expenditure and supply. […] However, it was the discovery of leptin and the genes regulating its production in adipocytes that caused a revolution in our understanding of intake-expenditure regulation and, thus, in the study of obesity. […] Regardless of the etiology of obesity, adequate knowledge of the mechanisms involved in the regulation of energy balance is essential for understanding the etiopathogenesis and pathophysiology of the increasing pandemic of obesity.

• #41 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology involves the complex interplay of genetic, environmental, and metabolic factors affecting energy balance and fat storage in the body. Dysregulation in hormones like leptin and insulin, along with inflammation, contributes to abnormal fat accumulation and chronic weight gain. Understanding obesity’s underlying mechanisms is crucial for developing effective obesity management and prevention strategies. […] Obesity is characterized by an imbalance between energy intake and energy expenditure. Various mechanisms contribute to this imbalance, including genetic, environmental, and psychological factors, leading to an increased body mass index (BMI). Key mechanisms include: Hypothalamic regulation: The hypothalamus plays a crucial role in managing hunger and energy balance. Dysfunctions in this area can lead to overeating and weight gain. Genetic predisposition: Some individuals have a genetic tendency to accumulate fat due to hereditary traits. Energy homeostasis: A disruption in the balance of energy consumed through food and energy expended through physical activity leads to obesity. Lipid metabolism disruption: Excessive fat storage in adipose tissue contributes to obesity, affecting how the body processes lipids.

• #42 Obesity and hormones | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones

  Body fat distribution plays an important role in the development of obesity-related conditions such as heart disease, stroke and some forms of arthritis. […] The pituitary gland in our brain produces growth hormone, which influences a person’s height and helps build bone and muscle. Growth hormone also affects metabolism (the rate at which we burn kilojoules for energy). Researchers have found that growth hormone levels in people who are obese are lower than in people of normal weight. […] Obesity is also associated with low-grade chronic inflammation within the fat tissue. Excessive fat storage leads to stress reactions within fat cells, which in turn lead to the release of pro-inflammatory factors from the fat cells themselves and immune cells within the adipose (fat) tissue. […] Obesity is associated with an increased risk of a number of diseases, including cardiovascular disease, stroke and several types of cancer, and with decreased longevity (shorter life span) and lower quality of life. […] Studies have also shown that weight loss as a result of healthy diet and exercise or bariatric surgery leads to improved insulin resistance, decreased inflammation and beneficial modulation of obesity hormones.

• #43 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  The role of the gut microbiota has emerged as a significant factor in obesity. The diversity and balance of gut microorganisms can influence fat storage, inflammatory reactions, and energy regulation. Recent research suggests that changes in gut flora composition can impact weight gain, making the microbiota a potential target for therapeutic interventions in obesity. […] Metabolic alterations are a hallmark of obesity pathophysiology. These alterations can affect various body systems, leading to numerous health issues. Here are important metabolic changes associated with obesity: Insulin resistance: A common feature, where body cells become less responsive to insulin, leading to higher blood sugar levels. Chronic inflammation: Excess fat, especially visceral fat, triggers an inflammatory response that affects metabolic health. Dyslipidemia: Characterized by abnormal lipid levels, including elevated triglycerides and decreased HDL (good cholesterol). Altered hormone levels: Leptin and ghrelin, hormones regulating appetite and satiety, can be dysregulated.

• #44 Mechanism of Acupuncture in Treating Obesity: Advances and Prospects | The American Journal of Chinese Medicine

  https://worldscientific.com/doi/10.1142/S0192415X24500010?srsltid=AfmBOoqIKYDq_PEhe3dw0m2QvMl_4gS8OKG5PV1nbhMFNvBrzIjMI878

  Acupuncture can significantly decrease Firmicutes abundance and enhance Bacteroidetes abundance, lowering the Firmicutes/Bacteroidetes ratio. […] Acupuncture plays an important role in improving obesity and obesity-related hepatic disorders by modulating oxidative stress and suppressing apoptosis in the liver. […] Acupuncture exerts beneficial effects via regulating the CNS, ANS, hormones, brain-gut axis, inflammation, adipose tissue, MBF, hypoxia, and ROS.

• #45 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Endocrine factors play a critical role in the development and maintenance of obesity. Hormones produced by endocrine glands can influence appetite, metabolism, and fat distribution. Key hormones involved include: Leptin: Produced by fat cells, it signals the brain to decrease appetite. However, in obesity, leptin resistance can occur, leading to uncontrolled hunger. Insulin: Beyond regulating blood glucose, insulin has an impact on fat storage and muscle energy utilization. Cortisol: Known as the stress hormone, excess cortisol can promote fat accumulation, particularly in the abdominal area. Thyroid hormones: These hormones regulate the body’s metabolism, and imbalances can lead to weight changes. […] The pathophysiology of childhood obesity involves multiple interrelated factors that contribute to excessive weight gain. These factors include: Genetic predispositions: Inherited traits can significantly impact a child’s likelihood of becoming obese. Environmental influences: The availability of unhealthy foods and sedentary lifestyles play crucial roles. Behavioral aspects: Habits developed during childhood, such as physical inactivity and poor dietary choices, establish the foundation for obesity.

• #46 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Endocrine factors play a critical role in the development and maintenance of obesity. Hormones produced by endocrine glands can influence appetite, metabolism, and fat distribution. Key hormones involved include: Leptin: Produced by fat cells, it signals the brain to decrease appetite. However, in obesity, leptin resistance can occur, leading to uncontrolled hunger. Insulin: Beyond regulating blood glucose, insulin has an impact on fat storage and muscle energy utilization. Cortisol: Known as the stress hormone, excess cortisol can promote fat accumulation, particularly in the abdominal area. Thyroid hormones: These hormones regulate the body’s metabolism, and imbalances can lead to weight changes. […] The pathophysiology of childhood obesity involves multiple interrelated factors that contribute to excessive weight gain. These factors include: Genetic predispositions: Inherited traits can significantly impact a child’s likelihood of becoming obese. Environmental influences: The availability of unhealthy foods and sedentary lifestyles play crucial roles. Behavioral aspects: Habits developed during childhood, such as physical inactivity and poor dietary choices, establish the foundation for obesity.

• #47 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Endocrine factors play a critical role in the development and maintenance of obesity. Hormones produced by endocrine glands can influence appetite, metabolism, and fat distribution. Key hormones involved include: Leptin: Produced by fat cells, it signals the brain to decrease appetite. However, in obesity, leptin resistance can occur, leading to uncontrolled hunger. Insulin: Beyond regulating blood glucose, insulin has an impact on fat storage and muscle energy utilization. Cortisol: Known as the stress hormone, excess cortisol can promote fat accumulation, particularly in the abdominal area. Thyroid hormones: These hormones regulate the body’s metabolism, and imbalances can lead to weight changes. […] The pathophysiology of childhood obesity involves multiple interrelated factors that contribute to excessive weight gain. These factors include: Genetic predispositions: Inherited traits can significantly impact a child’s likelihood of becoming obese. Environmental influences: The availability of unhealthy foods and sedentary lifestyles play crucial roles. Behavioral aspects: Habits developed during childhood, such as physical inactivity and poor dietary choices, establish the foundation for obesity.

• #48 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Endocrine factors play a critical role in the development and maintenance of obesity. Hormones produced by endocrine glands can influence appetite, metabolism, and fat distribution. Key hormones involved include: Leptin: Produced by fat cells, it signals the brain to decrease appetite. However, in obesity, leptin resistance can occur, leading to uncontrolled hunger. Insulin: Beyond regulating blood glucose, insulin has an impact on fat storage and muscle energy utilization. Cortisol: Known as the stress hormone, excess cortisol can promote fat accumulation, particularly in the abdominal area. Thyroid hormones: These hormones regulate the body’s metabolism, and imbalances can lead to weight changes. […] The pathophysiology of childhood obesity involves multiple interrelated factors that contribute to excessive weight gain. These factors include: Genetic predispositions: Inherited traits can significantly impact a child’s likelihood of becoming obese. Environmental influences: The availability of unhealthy foods and sedentary lifestyles play crucial roles. Behavioral aspects: Habits developed during childhood, such as physical inactivity and poor dietary choices, establish the foundation for obesity.

• #49 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Endocrine factors play a critical role in the development and maintenance of obesity. Hormones produced by endocrine glands can influence appetite, metabolism, and fat distribution. Key hormones involved include: Leptin: Produced by fat cells, it signals the brain to decrease appetite. However, in obesity, leptin resistance can occur, leading to uncontrolled hunger. Insulin: Beyond regulating blood glucose, insulin has an impact on fat storage and muscle energy utilization. Cortisol: Known as the stress hormone, excess cortisol can promote fat accumulation, particularly in the abdominal area. Thyroid hormones: These hormones regulate the body’s metabolism, and imbalances can lead to weight changes. […] The pathophysiology of childhood obesity involves multiple interrelated factors that contribute to excessive weight gain. These factors include: Genetic predispositions: Inherited traits can significantly impact a child’s likelihood of becoming obese. Environmental influences: The availability of unhealthy foods and sedentary lifestyles play crucial roles. Behavioral aspects: Habits developed during childhood, such as physical inactivity and poor dietary choices, establish the foundation for obesity.

• #50 Signaling pathways in obesity: mechanisms and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01149-x

  The TGF- superfamily consists of TGF-1-3, activins/inhibins, growth differentiation factors (GDFs), myostatin, and BMPs, playing diverse roles in appetite regulation, lipid metabolism, and glucose homeostasis. […] AMPK functions as a fuel gauge to monitor cellular energy status and is highly conserved across all eukaryotic species. […] The Wnt/-catenin pathway has been suggested to have a negative effect on adipogenesis and obesity. […] The activation/inhibition of the Wnt signaling pathway leads to different effects in obesity pathogenesis, which is determined by the specific pathways of action. […] ER stress refers to a condition in which unfolded or misfolded proteins accumulate in ER and leads to stress conditions. […] A plethora of evidence from animal and clinical studies shows that elevated ER stress in adipose tissue is induced by obesity, which in turn impairs ER functions and leads to metabolic dysfunction within the cell.

• #51 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  The role of the gut microbiota has emerged as a significant factor in obesity. The diversity and balance of gut microorganisms can influence fat storage, inflammatory reactions, and energy regulation. Recent research suggests that changes in gut flora composition can impact weight gain, making the microbiota a potential target for therapeutic interventions in obesity. […] Metabolic alterations are a hallmark of obesity pathophysiology. These alterations can affect various body systems, leading to numerous health issues. Here are important metabolic changes associated with obesity: Insulin resistance: A common feature, where body cells become less responsive to insulin, leading to higher blood sugar levels. Chronic inflammation: Excess fat, especially visceral fat, triggers an inflammatory response that affects metabolic health. Dyslipidemia: Characterized by abnormal lipid levels, including elevated triglycerides and decreased HDL (good cholesterol). Altered hormone levels: Leptin and ghrelin, hormones regulating appetite and satiety, can be dysregulated.

• #52 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  The role of the gut microbiota has emerged as a significant factor in obesity. The diversity and balance of gut microorganisms can influence fat storage, inflammatory reactions, and energy regulation. Recent research suggests that changes in gut flora composition can impact weight gain, making the microbiota a potential target for therapeutic interventions in obesity. […] Metabolic alterations are a hallmark of obesity pathophysiology. These alterations can affect various body systems, leading to numerous health issues. Here are important metabolic changes associated with obesity: Insulin resistance: A common feature, where body cells become less responsive to insulin, leading to higher blood sugar levels. Chronic inflammation: Excess fat, especially visceral fat, triggers an inflammatory response that affects metabolic health. Dyslipidemia: Characterized by abnormal lipid levels, including elevated triglycerides and decreased HDL (good cholesterol). Altered hormone levels: Leptin and ghrelin, hormones regulating appetite and satiety, can be dysregulated.

• #53 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  The role of the gut microbiota has emerged as a significant factor in obesity. The diversity and balance of gut microorganisms can influence fat storage, inflammatory reactions, and energy regulation. Recent research suggests that changes in gut flora composition can impact weight gain, making the microbiota a potential target for therapeutic interventions in obesity. […] Metabolic alterations are a hallmark of obesity pathophysiology. These alterations can affect various body systems, leading to numerous health issues. Here are important metabolic changes associated with obesity: Insulin resistance: A common feature, where body cells become less responsive to insulin, leading to higher blood sugar levels. Chronic inflammation: Excess fat, especially visceral fat, triggers an inflammatory response that affects metabolic health. Dyslipidemia: Characterized by abnormal lipid levels, including elevated triglycerides and decreased HDL (good cholesterol). Altered hormone levels: Leptin and ghrelin, hormones regulating appetite and satiety, can be dysregulated.

• #54 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  The role of the gut microbiota has emerged as a significant factor in obesity. The diversity and balance of gut microorganisms can influence fat storage, inflammatory reactions, and energy regulation. Recent research suggests that changes in gut flora composition can impact weight gain, making the microbiota a potential target for therapeutic interventions in obesity. […] Metabolic alterations are a hallmark of obesity pathophysiology. These alterations can affect various body systems, leading to numerous health issues. Here are important metabolic changes associated with obesity: Insulin resistance: A common feature, where body cells become less responsive to insulin, leading to higher blood sugar levels. Chronic inflammation: Excess fat, especially visceral fat, triggers an inflammatory response that affects metabolic health. Dyslipidemia: Characterized by abnormal lipid levels, including elevated triglycerides and decreased HDL (good cholesterol). Altered hormone levels: Leptin and ghrelin, hormones regulating appetite and satiety, can be dysregulated.

• #55 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  The role of the gut microbiota has emerged as a significant factor in obesity. The diversity and balance of gut microorganisms can influence fat storage, inflammatory reactions, and energy regulation. Recent research suggests that changes in gut flora composition can impact weight gain, making the microbiota a potential target for therapeutic interventions in obesity. […] Metabolic alterations are a hallmark of obesity pathophysiology. These alterations can affect various body systems, leading to numerous health issues. Here are important metabolic changes associated with obesity: Insulin resistance: A common feature, where body cells become less responsive to insulin, leading to higher blood sugar levels. Chronic inflammation: Excess fat, especially visceral fat, triggers an inflammatory response that affects metabolic health. Dyslipidemia: Characterized by abnormal lipid levels, including elevated triglycerides and decreased HDL (good cholesterol). Altered hormone levels: Leptin and ghrelin, hormones regulating appetite and satiety, can be dysregulated.

• #56 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology refers to the underlying mechanisms and factors leading to excessive fat accumulation in the body, impacting health and well-being. […] Recent advances in genetic research have identified specific gene mutations that could significantly impact the energy balance and appetite regulation in individuals with morbid obesity. Variations in these genes may lead to increased fat storage and difficulty in losing weight, highlighting potential targets for personalized treatments in severe obesity cases. […] The pathophysiological changes in morbid obesity result in numerous detrimental health impacts. These include: Cardiovascular diseases: The risk is substantially higher due to factors like hypertension and dyslipidemia. Type 2 diabetes: Enhanced insulin resistance directly links morbid obesity to a higher prevalence of diabetes. Sleep apnea: Excessive weight increases breathing difficulties during sleep. Osteoarthritis: The added weight places stress on joints, exacerbating wear and tear. Psychological effects: Including depression and decreased quality of life due to social and physical limitations.

• #57 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology refers to the underlying mechanisms and factors leading to excessive fat accumulation in the body, impacting health and well-being. […] Recent advances in genetic research have identified specific gene mutations that could significantly impact the energy balance and appetite regulation in individuals with morbid obesity. Variations in these genes may lead to increased fat storage and difficulty in losing weight, highlighting potential targets for personalized treatments in severe obesity cases. […] The pathophysiological changes in morbid obesity result in numerous detrimental health impacts. These include: Cardiovascular diseases: The risk is substantially higher due to factors like hypertension and dyslipidemia. Type 2 diabetes: Enhanced insulin resistance directly links morbid obesity to a higher prevalence of diabetes. Sleep apnea: Excessive weight increases breathing difficulties during sleep. Osteoarthritis: The added weight places stress on joints, exacerbating wear and tear. Psychological effects: Including depression and decreased quality of life due to social and physical limitations.

• #58 Obesity and hormones | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones

  Body fat distribution plays an important role in the development of obesity-related conditions such as heart disease, stroke and some forms of arthritis. […] The pituitary gland in our brain produces growth hormone, which influences a person’s height and helps build bone and muscle. Growth hormone also affects metabolism (the rate at which we burn kilojoules for energy). Researchers have found that growth hormone levels in people who are obese are lower than in people of normal weight. […] Obesity is also associated with low-grade chronic inflammation within the fat tissue. Excessive fat storage leads to stress reactions within fat cells, which in turn lead to the release of pro-inflammatory factors from the fat cells themselves and immune cells within the adipose (fat) tissue. […] Obesity is associated with an increased risk of a number of diseases, including cardiovascular disease, stroke and several types of cancer, and with decreased longevity (shorter life span) and lower quality of life. […] Studies have also shown that weight loss as a result of healthy diet and exercise or bariatric surgery leads to improved insulin resistance, decreased inflammation and beneficial modulation of obesity hormones.

• #59 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology refers to the underlying mechanisms and factors leading to excessive fat accumulation in the body, impacting health and well-being. […] Recent advances in genetic research have identified specific gene mutations that could significantly impact the energy balance and appetite regulation in individuals with morbid obesity. Variations in these genes may lead to increased fat storage and difficulty in losing weight, highlighting potential targets for personalized treatments in severe obesity cases. […] The pathophysiological changes in morbid obesity result in numerous detrimental health impacts. These include: Cardiovascular diseases: The risk is substantially higher due to factors like hypertension and dyslipidemia. Type 2 diabetes: Enhanced insulin resistance directly links morbid obesity to a higher prevalence of diabetes. Sleep apnea: Excessive weight increases breathing difficulties during sleep. Osteoarthritis: The added weight places stress on joints, exacerbating wear and tear. Psychological effects: Including depression and decreased quality of life due to social and physical limitations.

• #60 Pathogenesis of Obesity – Page 2

  https://www.medscape.com/viewarticle/412685_2

  Fat distribution and total fat mass both play a role in insulin resistance. Persons with central obesity, the android pattern that tends to be associated with particularly large visceral adipose tissue deposits, have higher insulin levels. Higher insulin levels are due to greater insulin resistance from increased body fat mass alone and also to decreased insulin clearance by the liver. […] Many published studies have demonstrated an association between upper body fat distribution and a higher probability of developing diabetes and cardiovascular disease independent of weight. This would point to central obesity as an independent risk factor. […] In obese patients, even before the development of frank type 2 diabetes, all of these post-receptor steps are slowed. Caro and colleagues have shown that insulin receptor kinase activation is already greatly decreased in obese individuals before they become diabetic, and highly impaired in obese diabetic persons. Other postbinding defects that have been described in patients with type 2 diabetes also occur in obese patients before diabetes has developed: impaired generation of insulin’s second messenger(s); impaired glucose transporter translocation; impaired cellular glucose entry; impaired glucose oxidation; and impaired glucose storage as glycogen.

• #61 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology refers to the underlying mechanisms and factors leading to excessive fat accumulation in the body, impacting health and well-being. […] Recent advances in genetic research have identified specific gene mutations that could significantly impact the energy balance and appetite regulation in individuals with morbid obesity. Variations in these genes may lead to increased fat storage and difficulty in losing weight, highlighting potential targets for personalized treatments in severe obesity cases. […] The pathophysiological changes in morbid obesity result in numerous detrimental health impacts. These include: Cardiovascular diseases: The risk is substantially higher due to factors like hypertension and dyslipidemia. Type 2 diabetes: Enhanced insulin resistance directly links morbid obesity to a higher prevalence of diabetes. Sleep apnea: Excessive weight increases breathing difficulties during sleep. Osteoarthritis: The added weight places stress on joints, exacerbating wear and tear. Psychological effects: Including depression and decreased quality of life due to social and physical limitations.

• #62 Epidemiology and pathogenesis of obesity hypoventilation syndrome – UpToDate

  https://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-obesity-hypoventilation-syndrome/print

  Obesity hypoventilation syndrome (OHS; „Pickwickian syndrome”) is defined as the presence of awake alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg) in an obese individual (body mass index ≥30 kg/m2) that cannot be attributed to other conditions associated with alveolar hypoventilation (eg, neuromuscular disorders) [1-3]. […] The pathogenesis of OHS is reviewed here.

• #63

  https://www.cnic.es/en/noticias/nature-metabolism-cnic-researchers-discover-mechanism-allowing-immune-cells-regulate

  These inflammation processes sourced to macrophages -says Dr. Enrquez- are responsible for the emergence of fatty tissue alterations, and are the origin of obesity and the metabolic syndrome associated to cardiovascular disorders, fatty liver disease and type 2 diabetes. […] This means that, as a response to the excess nutrients created by a high-fat diet macrophages change their function and support inflammatory processes, forming 'type M1′ proinflammatory macrophages. […] The research now published has analyzed how macrophage metabolic changes regulate this inflammatory process, which underlies obesity and the metabolic syndrome. […] This oxidative stress -she clarifies- is found in morbidly obese patients, and it seems to be related to a high-fat diet, commonplace in the inadequate Western diet.

• #64 Mechanism of Acupuncture in Treating Obesity: Advances and Prospects | The American Journal of Chinese Medicine

  https://worldscientific.com/doi/10.1142/S0192415X24500010?srsltid=AfmBOoqIKYDq_PEhe3dw0m2QvMl_4gS8OKG5PV1nbhMFNvBrzIjMI878

  Acupuncture can significantly decrease Firmicutes abundance and enhance Bacteroidetes abundance, lowering the Firmicutes/Bacteroidetes ratio. […] Acupuncture plays an important role in improving obesity and obesity-related hepatic disorders by modulating oxidative stress and suppressing apoptosis in the liver. […] Acupuncture exerts beneficial effects via regulating the CNS, ANS, hormones, brain-gut axis, inflammation, adipose tissue, MBF, hypoxia, and ROS.

• #65 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology refers to the underlying mechanisms and factors leading to excessive fat accumulation in the body, impacting health and well-being. […] Recent advances in genetic research have identified specific gene mutations that could significantly impact the energy balance and appetite regulation in individuals with morbid obesity. Variations in these genes may lead to increased fat storage and difficulty in losing weight, highlighting potential targets for personalized treatments in severe obesity cases. […] The pathophysiological changes in morbid obesity result in numerous detrimental health impacts. These include: Cardiovascular diseases: The risk is substantially higher due to factors like hypertension and dyslipidemia. Type 2 diabetes: Enhanced insulin resistance directly links morbid obesity to a higher prevalence of diabetes. Sleep apnea: Excessive weight increases breathing difficulties during sleep. Osteoarthritis: The added weight places stress on joints, exacerbating wear and tear. Psychological effects: Including depression and decreased quality of life due to social and physical limitations.

• #66 Obesity and hormones | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/healthyliving/obesity-and-hormones

  Body fat distribution plays an important role in the development of obesity-related conditions such as heart disease, stroke and some forms of arthritis. […] The pituitary gland in our brain produces growth hormone, which influences a person’s height and helps build bone and muscle. Growth hormone also affects metabolism (the rate at which we burn kilojoules for energy). Researchers have found that growth hormone levels in people who are obese are lower than in people of normal weight. […] Obesity is also associated with low-grade chronic inflammation within the fat tissue. Excessive fat storage leads to stress reactions within fat cells, which in turn lead to the release of pro-inflammatory factors from the fat cells themselves and immune cells within the adipose (fat) tissue. […] Obesity is associated with an increased risk of a number of diseases, including cardiovascular disease, stroke and several types of cancer, and with decreased longevity (shorter life span) and lower quality of life. […] Studies have also shown that weight loss as a result of healthy diet and exercise or bariatric surgery leads to improved insulin resistance, decreased inflammation and beneficial modulation of obesity hormones.

• #67 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Obesity pathophysiology refers to the underlying mechanisms and factors leading to excessive fat accumulation in the body, impacting health and well-being. […] Recent advances in genetic research have identified specific gene mutations that could significantly impact the energy balance and appetite regulation in individuals with morbid obesity. Variations in these genes may lead to increased fat storage and difficulty in losing weight, highlighting potential targets for personalized treatments in severe obesity cases. […] The pathophysiological changes in morbid obesity result in numerous detrimental health impacts. These include: Cardiovascular diseases: The risk is substantially higher due to factors like hypertension and dyslipidemia. Type 2 diabetes: Enhanced insulin resistance directly links morbid obesity to a higher prevalence of diabetes. Sleep apnea: Excessive weight increases breathing difficulties during sleep. Osteoarthritis: The added weight places stress on joints, exacerbating wear and tear. Psychological effects: Including depression and decreased quality of life due to social and physical limitations.

• #68 Digital Commons@NLU

  https://digitalcommons.nl.edu/diss/799/

  The obesity epidemic is a wicked problem with a complex web of determinants and outcomes. […] Much research evidence that a profusion of determinants of health support obesity pathogenesis through various physiological processes and mechanisms, including the allostatic load, mitochondria functioning, the gut microbiome, and epigenetics. […] This research suggests that chronic stress may put an individual at higher risk of internalizing weight stigma, which supports increased BMI. […] Together, these findings may be interpreted to support the requirement for multidisciplinary, trauma-informed treatment protocols capable of addressing the mental precursors and repercussions of the disease. Obesity treatment policies and protocols must strive to eliminate stigmatic practices, language, and aspects of the environment to better support individuals to reach their weight goals.

• #69 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Innovations in research have identified various mechanisms integral to understanding obesity pathophysiology. These discoveries include: Brown adipose tissue (BAT) activation: Recent studies show that activating BAT, which burns calories, contrasts the storage function of white adipose tissue. Genetic variations: New gene variants have been linked to obesity, offering potential targets for personalized treatment. Gut-brain axis: The interaction between gut bacteria and brain pathways influences hunger and weight regulation. Immune system involvement: Immune cells in adipose tissue contribute to inflammation, influencing obesity development.

• #70 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Innovations in research have identified various mechanisms integral to understanding obesity pathophysiology. These discoveries include: Brown adipose tissue (BAT) activation: Recent studies show that activating BAT, which burns calories, contrasts the storage function of white adipose tissue. Genetic variations: New gene variants have been linked to obesity, offering potential targets for personalized treatment. Gut-brain axis: The interaction between gut bacteria and brain pathways influences hunger and weight regulation. Immune system involvement: Immune cells in adipose tissue contribute to inflammation, influencing obesity development.

• #71 Mechanism Explaining Obesity Paradox Uncovered

  https://www.genengnews.com/news/mechanism-explaining-obesity-paradox-uncovered/

  Understanding how the body responds to excess weight and body fat is essential for combating the numerous ill effects of obesity. […] The mechanism we have identified here could be one of many that protect the heart in obesity. […] We have found that adipocytes respond to mitochondrial stress by rapidly and robustly releasing small extracellular vesicles (sEVs). […] These sEVs contain respiration-competent, but oxidatively damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes, where they trigger a burst of ROS. […] This study provides the first description of functional mitochondrial transfer between tissues and the first vertebrate example of „inter-organ mitohormesis.” […] Thus, these seemingly toxic adipocyte sEVs may provide a physiological avenue of potent cardioprotection against the inevitable lipotoxic or ischemic stresses elicited by obesity.

• #72 Mechanism behind obesity-related asthma identified | Harvard T.H. Chan School of Public Health

  https://hsph.harvard.edu/news/obesity-asthma-mechanism/

  Obesity-related asthma is poorly understood and very difficult to manage. […] Obesity is both a risk factor and a disease modifier for asthma, in that obesity increases the risk of developing asthma and asthma patients with obesity tend to have more symptoms and more exacerbations, and do not respond well to several standard asthma medications. […] We found that a hormone called cholecystokinin contributes in part to the airway narrowing that results in airflow limitation in obesity-related asthma. […] We now provide evidence that cholecystokinin and CCKAR are involved in obesity-induced airway narrowing. The mechanism behind obesity-related asthma has been poorly understood, so this is a big step in the research. […] Yes, we found that existing pharmacological compounds that block CCKAR, known as CCKAR antagonists (proglumide, lorglumide, and devazepide), could lower asthma symptoms in obese mice.

• #73 Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora

  https://www.mdpi.com/2227-9059/12/8/1633

  Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. […] Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. […] DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. […] The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. […] Research has revealed that alterations in DNA methylation patterns, induced by high-calorie diets and sedentary lifestyles, can affect the expression of genes involved in energy metabolism and fat storage, ultimately promoting the onset of obesity.

• #74 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Innovations in research have identified various mechanisms integral to understanding obesity pathophysiology. These discoveries include: Brown adipose tissue (BAT) activation: Recent studies show that activating BAT, which burns calories, contrasts the storage function of white adipose tissue. Genetic variations: New gene variants have been linked to obesity, offering potential targets for personalized treatment. Gut-brain axis: The interaction between gut bacteria and brain pathways influences hunger and weight regulation. Immune system involvement: Immune cells in adipose tissue contribute to inflammation, influencing obesity development.

• #75 Broken Energy Homeostasis and Obesity Pathogenesis: The Surrounding Concepts

  https://www.mdpi.com/2077-0383/7/11/453

  Obesity represents an abnormal fat accumulation resulting from energy imbalances. […] Therefore, within this review we report selected illustrative examples of the underlying mechanisms beyond the obesity pathogenesis which is systemic rather than limited to fat accumulation. […] Understanding obesity through the underlying pathway changes will allow us to overcome the main challenge facing obesity studies, which includes explaining the etiologies and mechanisms of obesity linking molecular and cellular modifications to the clinical outcomes. […] The gut-brain axis and metabolic hormones represent the best illustrations. […] The „deregulation” of the gut-brain axis might be the starting point for obesity pathogenesis, rather than an adaptive consequence. […] Importantly, since a neuro-endocrine system that controls energy homeostasis exists, how can some individuals still develop obesity?

• #76 Obesity Pathophysiology: Metabolic Mechanisms | Vaia

  https://www.vaia.com/en-us/explanations/medicine/pathology-histology/obesity-pathophysiology/

  Innovations in research have identified various mechanisms integral to understanding obesity pathophysiology. These discoveries include: Brown adipose tissue (BAT) activation: Recent studies show that activating BAT, which burns calories, contrasts the storage function of white adipose tissue. Genetic variations: New gene variants have been linked to obesity, offering potential targets for personalized treatment. Gut-brain axis: The interaction between gut bacteria and brain pathways influences hunger and weight regulation. Immune system involvement: Immune cells in adipose tissue contribute to inflammation, influencing obesity development.

• #77

  https://www.cnic.es/en/noticias/nature-metabolism-cnic-researchers-discover-mechanism-allowing-immune-cells-regulate

  The results published in Nature Metabolism could be useful to design new treatments for the obese and overweight, and for some associated pathologies, including fatty liver disease and type 2 diabetes. […] Now, researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have shown how this regulation unfolds in a paper published in Nature Metabolism, which could be useful to design new treatments for the obese and overweight, and for some associated pathologies, including fatty liver disease and type 2 diabetes. […] The study was led by CNIC researchers directed by Dr. Jos Antonio Enrquez and Dr. David Sancho. […] It explains how the activation of the mitochondrial metabolism of macrophages in response to oxidative stress due to excess nutrients contributes to fatty tissue inflammation and obesity.

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