Physiological Conditions, Bioactive Ingredients, and Drugs Stimulating Non-Shivering Thermogenesis as a Promising Treatment Against Diabesity
Abstract
Obesity (lipotoxicity) results from a chronic imbalance between energy intake and expenditure. It is strongly associated with type 2 diabetes mellitus (T2DM, glucotoxicity) and considered a major risk factor for the development of metabolic complications. Their convergence constitutes "diabesity", representing a major challenge for public health worldwide. Limited treatment efficacy highlights the need for novel, multi-targeted therapies. Non-shivering thermogenesis (NST), mediated by brown and beige adipose tissue and skeletal muscle, has emerged as a promising therapy due to its capacity to increase energy expenditure and improve metabolic health. Also, skeletal muscle plays a central role in glucose uptake and lipid oxidation, further highlighting its relevance in diabesity. This review explores current and emerging knowledge on physiological stimuli, including cold exposure, physical activity, and fasting, as well as bioactive ingredients and drugs that stimulate NST in thermogenic tissues. Special emphasis is placed on melatonin as a potential regulator of mitochondrial function and energy balance. The literature search was conducted using MEDLINE and Web of Science. Studies were selected based on scientific relevance, novelty, and mechanistic insight; prioritizing human and high-quality rodent research published in peer-reviewed journals. Evidence shows that multiple interventions enhance NST, leading to improved glucose metabolism, reduced fat accumulation, and…
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Evidence Hub reads this as a review, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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