Obesogens: a unifying theory for the global rise in obesity

International Journal of Obesity, Journal Year: 2024, Volume and Issue: 48(4), P. 449 - 460

Published: Jan. 11, 2024

Despite varied treatment, mitigation, and prevention efforts, the global prevalence severity of obesity continue to worsen. Here we propose a combined model obesity, unifying paradigm that links four general models: energy balance (EBM), based on calories as driver weight gain; carbohydrate-insulin (CIM), insulin storage; oxidation-reduction (REDOX), reactive oxygen species (ROS) altered metabolic signaling; obesogens (OBS), which proposes environmental chemicals interfere with hormonal signaling leading adiposity. We OBS/REDOX in (in air, food, food packaging, household products) generate false autocrine endocrine signals, including ROS, subvert standard regulatory mechanisms, increase basal stimulated secretion, disrupt efficiency, influence appetite expenditure gain. This incorporates data supporting EBM CIM models, thus creating one integrated covers significant aspects all mechanisms potentially contributing pandemic. Importantly, provides rationale approach for future preventative efforts chemical exposure reduction.

Language: Английский

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Disorders of Lipid Metabolism

Published: Jan. 1, 2024

Language: Английский

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Metabolic memory: mechanisms and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 28, 2024

Metabolic diseases and their complications impose health economic burdens worldwide. Evidence from past experimental studies clinical trials suggests our body may have the ability to remember metabolic environment, such as hyperglycemia or hyperlipidemia, thus leading chronic inflammatory disorders other even after elimination of these environments. The long-term effects that aberrant metabolism on been summarized memory are found assume a crucial role in states disease. Multiple molecular mechanisms collectively participate management, resulting different cellular alterations well tissue organ dysfunctions, culminating disease progression affecting offspring. elucidation expansion concept provides more comprehensive insight into pathogenic underlying promises be new target detection management. Here, we retrace history relevant research summarize its salient characteristics. We provide detailed discussion by which involved development at molecular, cellular, levels, with emphasis impact epigenetic modulations. Finally, present some pivotal findings arguing favor targeting develop therapeutic strategies for latest reflections consequences implications human diseases.

Language: Английский

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Sex-Specific Factors Influencing Obesity in Women: Bridging the Gap Between Science and Clinical Practice

Circulation Research, Journal Year: 2025, Volume and Issue: 136(6), P. 594 - 605

Published: March 13, 2025

Obesity in women is a significant public health issue with serious implications for cardiovascular-kidney-metabolic syndrome and cardiovascular disease. This complex challenge influenced by physiological, hormonal, socioeconomic, cultural factors. Women face unique weight management challenges due to hormonal changes during pregnancy, perimenopause, menopause, which affect fat distribution increase risk. Current clinical guidelines often overlook these sex-specific factors, potentially limiting the effectiveness of obesity strategies women. review explores aspects obesity’s pathophysiology, epidemiological trends, associated comorbidities, focusing on metabolic complications. synthesizes literature women, emphasizing factors influencing its development progression. It examines limitations body mass index as an measure alternative classification methods. Additionally it investigates relationship between comorbidities such diabetes, hypertension, dyslipidemia, focus postmenopausal linked increased risks Hormonal fluctuations throughout life contribute gain patterns specific increasing disease Effective must account variations. Postmenopausal are particularly affected obesity-related Lifestyle interventions, pharmacotherapy, bariatric surgery have shown efficacy management, though success rates vary. Addressing requires comprehensive approach that considers physiological life-stage challenges, sociocultural barriers. Integrating precision medicine emerging therapies offers potential more personalized effective interventions. Personalized consider women’s biological can enhance improve outcomes. Future research practice should developing tailored address vulnerabilities validating interventions

Language: Английский

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Time to Consider the “Exposome Hypothesis” in the Development of the Obesity Pandemic

Nutrients, Journal Year: 2022, Volume and Issue: 14(8), P. 1597 - 1597

Published: April 12, 2022

The obesity epidemic shows no signs of abatement. Genetics and overnutrition together with a dramatic decline in physical activity are the alleged main causes for this pandemic. While they undoubtedly represent contributors to problem, not able fully explain all cases current trends. In context, body knowledge related exposure as yet underappreciated obesogenic factors, which can be referred "exposome", merits detailed analysis. Contrarily genome, "exposome" is subject great dynamism variability, unfolds throughout individual's lifetime. development precise ways capturing full spectrum person extraordinarily demanding. Data derived from epidemiological studies linking excess weight elevated ambient temperatures, utero, intergenerational effects well epigenetics, microorganisms, microbiota, sleep curtailment, endocrine disruptors, among others, suggests possibility that may work alone or synergistically several alternative putative global epidemic. This narrative review reports available evidence on drivers Broadly based interventions needed better identify these at same time stimulating reflection potential relevance perpetuation

Language: Английский

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Hypertension Related to Obesity: Pathogenesis, Characteristics and Factors for Control

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12305 - 12305

Published: Oct. 14, 2022

The World Health Organization (WHO) refers to obesity as abnormal or excessive fat accumulation that presents a health risk. Obesity was first designated disease in 2012 and since then the cost burden of have witnessed worrisome increase. hypertension are closely interrelated abdominal interferes with endocrine immune systems carries greater risk for insulin resistance, diabetes, hypertension, cardiovascular disease. Many factors at interplay between hypertension. They include hemodynamic alterations, oxidative stress, renal injury, hyperinsulinemia, sleep apnea syndrome leptin-melanocortin pathway. Genetics, epigenetics, mitochondrial also play major role. measurement blood pressure obese patients requires an adapted cuff search other secondary causes is necessary higher thresholds than general population. Lifestyle modifications such diet exercise often not enough control obesity, so far, bariatric surgery constitutes most reliable method achieve weight loss. Nonetheless, emergence new agents Semaglutide Tirzepatide offers promising alternatives. Finally, several molecular pathways actively being explored, they should significantly extend treatment options available.

Language: Английский

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The Role of Obesity and Diabetes in Dementia

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9267 - 9267

Published: Aug. 17, 2022

Chronic conditions such as obesity, diabetes, and dementia are increasing in the United States (US) population. Knowledge of these chronic conditions, preventative measures, proper management tactics is important critical to preventing disease. The overlap between becoming further elucidated. These share a similar origin through components age, gender, genetic epigenetic predispositions, depression, high-fat Western diet (WD) that all contribute inflammatory state associated with development dementia. This leads dysregulation food intake insulin resistance. Obesity often cornerstone diabetes and, subsequently, case type 2 mellitus (T2DM), progression "type 3 (T3DM)". depression closely diabetes. However, can be avoided lifestyle modifications, by switching plant-based (e.g., Mediterranean (MD)), physical activity. Diet exercise not only treatment options. There several surgical pharmacological interventions available for prevention. Current future research within each fields warranted offers chance new options better understanding pathogenesis condition.

Language: Английский

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Genetics, epigenetics and transgenerational transmission of obesity in children

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 14, 2022

Sedentary lifestyle and consumption of high-calorie foods have caused a relentless increase overweight obesity prevalence at all ages. Its presently epidemic proportion is disquieting due to the tight relationship with metabolic syndrome several other comorbidities which do call for urgent workarounds. The usual ineffectiveness present therapies failure prevention campaigns triggered overtime number research studies unveiled some relevant aspects genetic epigenetic inheritable profiles. These findings are revealing extremely precious mainly serve as likely extra arrow allow clinician’s bow achieve still hitherto unmet preventive goals. Evidence now exists that maternal obesity/overnutrition during pregnancy lactation convincingly appears associated disorders in offspring independently transmission purely predisposition. Even pre-conception direct exposure either father or mother gametes environmental factors can reprogram architecture cells. Such phenomena lie behind transfer susceptibility future generations through mechanism inheritance. Moreover, growing suggests such malnutrition, hypoxia, excess hormones endocrine disruptors early postnatal period may play critical roles programming childhood adipose tissue obesity. A deeper understanding how inherited genetics epigenetics generate an obesogenic environment pediatric age might strengthen our knowledge about pathogenetic mechanisms improve clinical management patients. Therefore, this narrative review, we attempt provide general overview contribution heritable patterns children, placing particular emphasis on mother-child dyad.

Language: Английский

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Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9818 - 9818

Published: June 6, 2023

The comprehensive anabolic effects of insulin throughout the body, in addition to control glycemia, include ensuring lipid homeostasis and anti-inflammatory modulation, especially adipose tissue (AT). prevalence obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has been increasing worldwide on pandemic scale with accompanying syndemic health problems, including glucose intolerance, resistance (IR), diabetes. Impaired sensitivity or IR paradoxically leads diseases an inflammatory component despite hyperinsulinemia. Therefore, excess visceral AT obesity initiates chronic low-grade conditions that interfere signaling via receptors (INSRs). Moreover, response IR, hyperglycemia itself stimulates primarily defensive associated subsequent release numerous cytokines real threat organ function deterioration. In this review, all components vicious cycle are characterized particular emphasis interplay between both innate adaptive immune responses related obesity. Increased accumulation should be considered main environmental factor responsible for disruption epigenetic regulatory mechanisms system, resulting autoimmunity inflammation.

Language: Английский

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Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Endometriosis is defined as the presence of endometrial-like glands and stroma located outside uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% reproductive-aged women a well-recognized cause chronic pelvic pain infertility. Despite still unknown etiology endometriosis, much evidence suggests participation epigenetic mechanisms in disease etiopathogenesis. The main rationale based on fact that heritable phenotype changes do not involve alterations DNA sequence are common triggers for hormonal, immunological, disorders, which play key role formation endometriotic foci. Epigenetic regulating T-cell responses, including methylation posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work concert with organ structural cells generate appropriate immune responses functionally shaped by organ-specific environmental conditions. Thus, failure precisely regulate cell transcription may result compromised immunological integrity an increased risk disorders. coexistence endometriosis autoimmunity well-known occurrence. Recent research results indicate regulatory (Treg) number highly active Tregs macrophages have been found peritoneal fluid from endometriosis. Elimination function imbalance between helper Th1 Th2 types reported endometria endometriosis-associated review aims present state art recognition reprogramming factor pathophysiology context T-cell-related autoimmunity. new potential therapeutic approaches modulation and/or adoptive transfer will also be outlined.

Language: Английский

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