Abstract
Overweight and obesity are characterized by excessive fat mass accumulation produced when energy intake exceeds energy expenditure. One plausible way to control energy expenditure is to modulate thermogenic pathways in white adipose tissue (WAT) and/or brown adipose tissue (BAT). Among the different environmental factors capable of influencing host metabolism and energy balance, the gut microbiota is now considered a key player. Following pioneering studies showing that mice lacking gut microbes (that is, germ-free mice) or depleted of their gut microbiota (that is, using antibiotics) developed less adipose tissue, numerous studies have investigated the complex interactions existing between gut bacteria, some of their membrane components (that is, lipopolysaccharides), and their metabolites (that is, short-chain fatty acids, endocannabinoids, bile acids, aryl hydrocarbon receptor ligands and tryptophan derivatives) as well as their contribution to the browning and/or beiging of WAT and changes in BAT activity. In this Review, we discuss the general physiology of both WAT and BAT. Subsequently, we introduce how gut bacteria and different microbiota-derived metabolites, their receptors and signalling pathways can regulate the development of adipose tissue and its metabolic capacities. Finally, we describe the key challenges in moving from bench to bedside by presenting specific key examples.
Key points
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Approximately 40% of the global population is affected by overweight or obesity; novel treatments focusing on modulating thermogenic pathways in adipose tissue and altering gut microbiota are being explored.
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Adipose tissues, categorized as white, brown and beige, have distinct roles in energy storage, thermogenesis and metabolism in the body.
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Environmental factors substantially influence energy metabolism, with diet, exercise and sleep being primary contributors.
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Gut bacteria are involved in bidirectional communication between the gut and adipose tissue, influencing energy metabolism, nutrient absorption, appetite and adipose tissue function.
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Adipose tissue hosts its own distinct microbiota, which varies based on metabolic health and other factors; its understanding could offer novel insights.
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Translating gut microbiota research from animal models to human applications faces methodological and biological challenges.
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Acknowledgements
P.D.C. is Honorary Research Director at FRS-FNRS (Fonds de la Recherche Scientifique) and a recipient of grants from FNRS (Projet de Recherche PDR-convention: FNRS T.0030.21, CDR-convention: J.0027.22, FRFS-WELBIO: WELBIO-CR-2022A-02, EOS: programme no. 40007505) and ARC (action de recherche concertée: ARC19/24-096) and La Caixa (NeuroGut).
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P.D.C. is an inventor on patent applications dealing with the use of specific bacteria and components in the treatment of different diseases. P.D.C. was co-founder of The Akkermansia Company SA and Enterosys. M.V.H. declares no competing interests.
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Cani, P.D., Van Hul, M. Gut microbiota in overweight and obesity: crosstalk with adipose tissue. Nat Rev Gastroenterol Hepatol 21, 164–183 (2024). https://doi.org/10.1038/s41575-023-00867-z
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DOI: https://doi.org/10.1038/s41575-023-00867-z
