@misc{10481/106857,
year = {2025},
month = {8},
url = {https://hdl.handle.net/10481/106857},
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
increased energy expenditure in humans and/or rodents. Melatonin, in particular, shows
promise in modulating thermogenesis through organelle-molecular pathways and mitochondrial protective effects. In conclusion, a multi-target approach through the activation
of NST by physiological, nutritional, and pharmacological agents offers an effective and
safe treatment for diabesity. Further research is needed to confirm these effects in clinical
practice and support their use as effective therapeutic strategies.},
organization = {MCIN/AEI/10.13039/501100011033/ - ERDF, EU (PID 2021-125900OB-I00)},
publisher = {MDPI},
keywords = {Obesity},
keywords = {diabetes mellitus},
keywords = {Type 2},
title = {Physiological Conditions, Bioactive Ingredients, and Drugs Stimulating Non-Shivering Thermogenesis as a Promising Treatment Against Diabesity},
doi = {10.3390/ph18091247},
author = {Salagre Simón, Diego and Ayala-Mosqueda, Ciskey V. and Aouichat, Samira and Agil Abdalla, Mhmad Ahmad},
}