Loss of CTRP10 results in female obesity with preserved metabolic health DOI Open Access
Fangluo Chen, Dylan C. Sarver,

Muzna Saqib

et al.

Published: March 6, 2025

Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain metabolic profile free syndrome. The molecular underpinnings MHO, however, not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent unique female model MHO. CTRP10 modulates weight gain in striking sexually dimorphic manner. Female, but male, lacking develop obesity with age on low-fat diet while maintaining an otherwise profile. When fed obesogenic diet, Ctrp10 knockout (KO) show rapid gain. Despite pronounced obesity, KO do steatosis, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. largely uncoupled from dysregulation mice. Multi-tissue transcriptomic analyses highlighted gene expression changes pathways associated insulin-sensitive obesity. Transcriptional correlation the differentially expressed (DEG) orthologous humans also shows sex differences connectivity within across tissues, underscoring conserved sex-dependent function CTRP10. Collectively, our findings suggest negatively regulates body females, loss results benign preserved sensitivity health. This MHO mouse valuable understanding sex-biased mechanisms uncouple dysfunction.

Language: Английский

Reassessing Human Adipose Tissue DOI
Aaron M. Cypess

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 386(8), P. 768 - 779

Published: Feb. 23, 2022

Adipose tissue can more than double in mass and then return to baseline. This review discusses the functional roles of human white brown adipose its excess obesity, as well far-reaching, complementary physiological endocrine system.

Language: Английский

Citations

284
Updates on obesity and the obesity paradox in cardiovascular diseases DOI

Austin W. Tutor,

Carl J. Lavie, Sergey Kachur

et al.

Progress in Cardiovascular Diseases, Journal Year: 2022, Volume and Issue: 78, P. 2 - 10

Published: Dec. 5, 2022

Language: Английский

Citations

141
Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity—The Case of BBS Obesity DOI Open Access

Avital Horwitz,

Ruth Birk

Nutrients, Journal Year: 2023, Volume and Issue: 15(15), P. 3445 - 3445

Published: Aug. 4, 2023

Obesity is a metabolic state generated by the expansion of adipose tissue. Adipose tissue depends on interplay between hyperplasia and hypertrophy, mainly regulated complex interaction genetics excess energy intake. However, genetic regulation yet to be fully understood. can divided into common multifactorial/polygenic obesity monogenic obesity, non-syndromic syndromic. Several genes related were found through studies models. syndromic characterized additional features other than suggesting more global role mutant syndrome and, thus, an peripheral influence development hardly studied date in this regard. This review summarizes present knowledge regarding hypertrophy adipocytes obesity. Additionally, we highlight scarce research as model for studying adipocyte focusing Bardet–Biedl (BBS). BBS involves central mechanisms, with molecular mechanistic alternation hypertrophy. Thus, argue that using models, such BBS, further advance our

Language: Английский

Citations

50
The Metabolic Syndrome, a Human Disease DOI Open Access
M. Alemany

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2251 - 2251

Published: Feb. 13, 2024

This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy associated diseases/disorders, or just related rather independent pathologies. The human nature MS (its exceptionality in Nature and its close interdependence with action evolution) is presented discussed. text also describes components, special emphasis description their interrelations (including syndromic development recruitment), as well consequences upon energy handling partition. main theories MS’s origin are relation to hepatic steatosis, type 2 diabetes, obesity, encompass most components described so far. differential effects sex biological considered under light social needs evolution, which directly epidemiology, severity, relations senescence. triggering maintenance factors discussed, especial inflammation, complex process affecting different levels organization critical element for development. Inflammation operation connective tissue adipose organ) widely studied acknowledged influence diet. role diet composition, including transcendence anaplerotic Krebs cycle from dietary amino acid supply (and timing), developed context testosterone β-estradiol control insulin-glycaemia core system carbohydrate-triacylglycerol handling. high probability acting unique (essentially monophyletic) presented, together additional perspectives/considerations treatment this ‘very’ disease.

Language: Английский

Citations

30
Precision Nutrition: Recent Advances in Obesity DOI
V. Saroja Voruganti

Physiology, Journal Year: 2022, Volume and Issue: 38(1), P. 42 - 50

Published: Sept. 20, 2022

"Precision nutrition" is an emerging area of nutrition research that focuses on understanding metabolic variability within and between individuals helps develop customized dietary plans interventions to maintain optimal individual health. It encompasses nutritional genomic (gene-nutrient interactions), epigenetic, microbiome, environmental factors. Obesity a complex disease affected by genetic factors thus relevant target precision nutrition-based approaches. Recent studies have shown significant associations obesity phenotypes (body weight, body mass index, waist circumference, central regional adiposity) variants, epigenetic (DNA methylation noncoding RNA), microbial species, environment (sociodemographics physical activity). Additionally, also the interactions metabolites, affect energy balance adiposity. These include variants in

Language: Английский

Citations

41
Current Treatments for Patients with Genetic Obesity DOI Creative Commons

Nathan Faccioli,

Christine Poitou, Karine Clément

et al.

Journal of Clinical Research in Pediatric Endocrinology, Journal Year: 2023, Volume and Issue: 15(2), P. 108 - 119

Published: May 16, 2023

Obesity derives from impaired central control of body weight, implying interaction between environment and an individual genetic predisposition.Genetic obesities, including monogenic syndromic are rare complex neuro-endocrine pathologies where the contribution is predominant.Severe early-onset obesity with eating disorders associated frequent comorbidities make these diseases challenging.Their current estimated prevalence 5-10% in severely obese children probably underestimated due to limited access diagnosis.A alteration hypothalamic regulation weight implies that leptin-melanocortin pathway responsible for symptoms.The management has so far been only based, above all, on lifestyle intervention, especially regarding nutrition physical activity.New therapeutic options have emerged last years patients, raising great hope manage their situation improve quality life.Implementation diagnosis clinical practice thus paramount importance allow individualized care.This review describes evidence which it based.Some insights will also be provided into new therapies under evaluation.

Language: Английский

Citations

34
Current and future pharmacotherapies for obesity in children and adolescents DOI
Aaron S. Kelly

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(9), P. 534 - 541

Published: June 19, 2023

Language: Английский

Citations

29
Genetics: A Starting Point for the Prevention and the Treatment of Obesity DOI Open Access
Giuseppe Novelli,

Carmen Cassadonte,

Paolo Sbraccia

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(12), P. 2782 - 2782

Published: June 17, 2023

Obesity is a common, serious, and costly disease. More than 1 billion people worldwide are obese—650 million adults, 340 adolescents, 39 children. The WHO estimates that, by 2025, approximately 167 people—adults children—will become less healthy because they overweight or obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes, certain types of cancer. These among the leading causes preventable, premature death. estimated annual medical cost obesity in United States was nearly $173 2019 dollars. considered result complex interaction between genes environment. Both environment change different populations. In fact, prevalence changes as eating habits, lifestyle, expression coding for factors involved regulation body weight, food intake, satiety. Expression these involves epigenetic processes, such DNA methylation, histone modification, non-coding micro-RNA synthesis, well variations gene sequence, which results functional alterations. Evolutionary non-evolutionary (i.e., genetic drift, migration, founder’s effect) have shaped predisposition protection from modern human Understanding knowing pathogenesis will lead to prevention treatment strategies not only obesity, but also other related diseases.

Language: Английский

Citations

23
Physical Activity and Incident Obesity Across the Spectrum of Genetic Risk for Obesity DOI Creative Commons
Evan L. Brittain, Lide Han, Jeffrey Annis

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(3), P. e243821 - e243821

Published: March 27, 2024

Importance Despite consistent public health recommendations, obesity rates in the US continue to increase. Physical activity recommendations do not account for individual genetic variability, increasing risk of obesity. Objective To use activity, clinical, and data from All Us Research Program (AoURP) explore association higher body mass index (BMI) with level physical needed reduce incident Design, Setting, Participants In this population–based retrospective cohort study, participants were enrolled AoURP between May 1, 2018, July 2022. Enrollees who European ancestry, owned a personal tracking device, did have up 6 months into included analysis. Exposure expressed as daily step counts polygenic score (PRS) BMI, calculated weight kilograms divided by height meters squared. Main Outcome Measures Incident (BMI ≥30). Results A total 3124 met inclusion criteria. Among 3051 available data, 2216 (73%) women, median age was 52.7 (IQR, 36.4-62.8) years. The walked 8326 6499-10 389) steps/d over 5.4 3.4-7.0) years tracking. incidence study period increased 13% (101 781) 43% (335 lowest highest PRS quartiles, respectively ( P = 1.0 × 10 −20 ). BMI demonstrated an 81% increase 3.57 ) while mean count reduction 5.30 −12 when comparing 75th 25th percentiles, respectively. Individuals percentile would need walk 2280 (95% CI, 1680-3310) more steps per day (11 020 total) than those at 50th comparable individuals PRS, baseline 22 additional 3460 steps/d; 24, 4430 26, 5380 28, 6350 steps/d. Conclusions Relevance across background quantified. Population-based may underestimate prevent among high risk.

Language: Английский

Citations

14
Potential mechanisms of precision nutrition-based interventions for managing obesity DOI Creative Commons
Neel H. Mehta, Samantha L. Huey, Rebecca Kuriyan

et al.

Advances in Nutrition, Journal Year: 2024, Volume and Issue: 15(3), P. 100186 - 100186

Published: Feb. 3, 2024

Precision nutrition (PN) considers multiple individual-level and environmental characteristics or variables, in order to better inform dietary strategies interventions for optimizing health, including managing obesity metabolic disorders. Here, we review the evidence on potential mechanisms – ones identify those most likely respond that can be leveraged development of PN addressing obesity. We conducted a literature included laboratory, animal, human studies evaluating biochemical genetic data, completed ongoing clinical trials, public programs this review. Our analysis describes related six domains predisposition; circadian rhythms; physical activity sedentary behavior; metabolomics; gut microbiome, behavioral socioeconomic characteristics; i.e. factors design PN-based prevent treat obesity-related outcomes such as weight loss health laid out by NIH 2030 Strategic Plan Nutrition Research. For example, single nucleotide polymorphisms (SNPs) modify responses certain interventions, epigenetic modulation risk via patterns macronutrient intake have also been demonstrated. Additionally, identified limitations questions equitable implementation across limited number trials. These include ability current address systemic influences supply chains food distribution, healthcare systems, racial cultural inequities, economic disparities particularly when designing implementing low- middle-income communities. has inter-individual variation, opposed "one-size fits all" standardized intervention, though there is trial date. Optimizing at individual level through microbiome assessment, lifestyle pattern analysis, phenotyping may help advance our modulate and/or manage individualized physiological involved

Language: Английский

Citations

9