On the pathogenesis of obesity: causal models and missing pieces of the puzzle

Nature Metabolism, Год журнала: 2024, Номер 6(10), С. 1856 - 1865

Опубликована: Авг. 20, 2024

Application of the physical laws energy and mass conservation at whole-body level is not necessarily informative about causal mechanisms weight gain development obesity. The balance model (EBM) carbohydrate-insulin (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework regulation human metabolism. These models have been used pathogenesis in individuals as well dramatic increases prevalence worldwide over past half century. Here, we summarize outcomes a recent workshop Copenhagen that brought together experts from around world discuss pathogenesis. discussions helped operationally define commonly terms; delineate structure each model, particularly focussing on areas overlap divergence; challenge ideas importance purported factors for gain; brainstorm key scientific questions need be answered. We hope more experimental research nutrition other related fields, testing their predictions will pave way provide answers than those currently available.

Язык: Английский

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Association among nesfatin-1, obesity category, presence of obesity-related complications, and eating patterns in patients with obesity: results of a single endocrine centre observational study

Peptides, Год журнала: 2025, Номер 185, С. 171355 - 171355

Опубликована: Фев. 5, 2025

Язык: Английский

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Holistic approaches to explain and combat obesity

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

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TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Abstract In mammals, the activation of thermogenic adipocytes, such as beige and brown can significantly increase overall energy expenditure, offering a promising strategy to combat metabolic diseases. Despite its considerable potential, regulatory mechanisms governing this remain largely elusive. This study bridges gap by elucidating that tripartite motif 56 (TRIM56), an E3 ubiquitin ligase, is upregulated in response cold stimuli, thereby promoting recruitment adipocytes. Notably, overexpression TRIM56 adipocytes shown help mice maintain core temperature under conditions, well confer protection against diet‐induced obesity. Mechanistically, facilitates degradation transducin‐like enhancer protein 3 (TLE3) K48‐linked ubiquitination, which subsequently triggers genes subcutaneousl white adipose tissue improved profiles. These findings unveil novel function for adipocyte browning, suggesting potential therapeutic target treatment disorders.

Язык: Английский

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Forecasting the global obesity epidemic through 2050

The Lancet, Год журнала: 2025, Номер 405(10481), С. 756 - 757

Опубликована: Март 1, 2025

Язык: Английский

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Testing the carbohydrate-insulin model: Short-term metabolic responses to consumption of meals with varying glycemic index in healthy adults

Cell Metabolism, Год журнала: 2025, Номер 37(3), С. 606 - 615.e3

Опубликована: Март 1, 2025

The carbohydrate-insulin model predicts that meals with varying glycemic indices will elicit distinct metabolic and hunger responses, including greater intake at subsequent following high-glycemic-index meals. To test this, a randomized trial (NCT05804942) was conducted in healthy adults using intervention low, medium, high constant macronutrient composition. After of the meals, glucose insulin followed predicted pattern, but subjective did not. At group level, low index led to lower energy changes. individual changes were unrelated body fatness or levels glucose, β-hydroxybutyrate, free fatty acids, L-lactate, leptin, adrenaline, glucagon-like peptide-1, glucagon, insulin-glucagon ratio. A weak negative association observed between ratio 300 min, opposite model's prediction. These data provide little support for model.

Язык: Английский

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Food insecurity promotes adiposity in mice

Obesity, Год журнала: 2025, Номер unknown

Опубликована: Март 23, 2025

Abstract Objective The obesity epidemic, driven by a complex interplay of environmental and biological factors, remains significant global health challenge. Herein, we investigate the impact food insecurity, characterized unpredictable access, on regulation body weight composition in mice. Methods Male female C57BL/6J mice were subjected to combination intermittent fasting calorie restriction simulate insecurity. Results Our new model demonstrates that insecurity increases fat mass decreases lean both sexes standard chow diet. Additionally, high‐fat diet‐fed male exposed paradigm show decreased despite being positive energy balance. Transcriptomic analysis white adipose tissue from food‐insecure revealed upregulation metabolic pathways associated with expansion downregulation immune response‐related transcripts. Conclusions These findings underscore role driving adaptations favor storage. Understanding this paradoxical link between adiposity is crucial for developing targeted interventions address disproportionate incidence socioeconomically disadvantaged populations.

Язык: Английский

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Obesity and nutritional strategies: advancing prevention and management through evidence-based approaches

Food and Agricultural Immunology, Год журнала: 2025, Номер 36(1)

Опубликована: Апрель 20, 2025

Язык: Английский

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Macronutrient interactions and models of obesity: Insights from nutritional geometry

BioEssays, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract The global obesity epidemic results from a complex interplay of genetic and environmental factors, with diet being prominent modifiable element driving weight gain adiposity. Although excess intake energetic macronutrients is implicated in causing obesity, ongoing debate centers on whether sugar or fat both are the rising rates. This has led to competing models such as “Carbohydrate Insulin Model”, “Energy Balance “Fructose Survival Hypothesis”. Conflicting evidence studies designed focus individual energy rather than macronutrient mixtures underlies this disagreement. Recent research humans animals employing nutritional geometry framework (NGF) emphasizes importance considering interactions among dietary components. Protein interacts carbohydrates, fats, density influence calorie (“protein leverage”) and, directly indirectly, metabolic physiology Consideration these can help reconcile different potentially cast new light interventions.

Язык: Английский

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Signals of energy availability in sleep: consequences of a fat-based metabolism

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Авг. 29, 2024

Humans can flexibly switch between two primary metabolic modes, usually distinguished by whether substrate supply from glucose meet energy demands or not. However, it is often overlooked that when use limited, the remainder of needs may still be met more less effectively with fat and ketone bodies. Hence a fat-based metabolism marked ketosis conflated starvation contexts inadequate (including at cellular level), even itself in ample supply. Sleep satiation are regulated common pathways reflecting metabolism. A conceptual analysis distinguishes signals glucose-dominant well sufficient allows reexamination experimental results study sleep shed light on species differences explain why ketogenic diets have beneficial effects simultaneously brain periphery. It also help to distinguish clinically failure diet resolve symptoms due rather than state itself.

Язык: Английский

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