The Crosstalk between Gut Microbiota and White Adipose Tissue Mitochondria in Obesity

Abstract

Adipose tissue (AT) dysregulation is a key process in the pathophysiology of obesity and its cardiometabolic complications, but even if a growing body of evidence has been collected over recent decades, the underlying molecular basis of adiposopathy remains to be fully understood. In this context, mitochondria, the intracellular organelles that orchestrate energy production and undergo highly dynamic adaptive changes in response to changing environments, have emerged as crucial regulators of both white (WAT) and brown adipose tissue (BAT) metabolism and function. Given that the gut microbiota and its metabolites are able to regulate host metabolism, adipogenesis, WAT inflammation, and thermogenesis, we hypothesize that their frequently observed dysregulation in obesity could affect AT metabolism by exerting direct and indirect effects on AT mitochondria. By collecting and revising the current evidence on the connections between gut microbiota and AT mitochondria in obesity, we gained insights into the molecular biology of their hitherto largely unexplored crosstalk, tracing how gut microbiota may regulate AT mitochondrial function.

Keywords: crosstalk; gut microbiota; mitochondria; obesity; white adipose tissue.

Figure 1

WAT, BAT, and WAT browning. White adipocyte has one large droplet in the centre of the cell that compresses nucleus and mitochondria at one pole. Brown adipocyte has multiple small lipid droplets and more mitochondria, spread out between the droplets. Beige adipocyte has intermediate characteristics. Cold exposure and β-adrenergic activation determine the browning of WAT. Both brown and beige mitochondria are involved in non-shivering thermogenesis. Created with BioRender.com (accessed on 13 March 2023). Abbreviations: BAT, brown adipose tissue; WAT, white adipose tissue.

Figure 2

Physiological functions of WAT mitochondria and common impairments in obesity. The left panel (in pink) refers to the physiological condition where some of the main functions of WAT mitochondria are presented. In the right panel (in grey), the same functions are impaired in obesity. Created with BioRender.com (accessed on 13 March 2023). Abbreviations: BCAAs, branched-chain amino acids; BCAT, branche- chain amino acid aminotransferase; OXPHOS, oxidative phosphorylation; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1α; PPARγ, peroxisome proliferator activated receptor-γ; ROS, reactive oxygen species.

Figure 3

Gut microbiota and microbial metabolites’ influence on WAT mitochondria in obesity. The interplay between gut microbiota and WAT mitochondria is mediated by microbial metabolites such as SCFAs, LPS, BCAAs, tryptophan, and trimethylamine. Among these, SCFAs are the most studied. Interestingly, modulating WAT browning is one of the most frequently reported effects of many microbial metabolites on WAT mitochondria. Created with BioRender.com (accessed on 13 March 2023). Abbreviations: BAT, brown adipose tissue; FMO3, flavin-containing monooxygenase 3; FOXc2, Forkhead box C2; miR-181, micro-RNA 181; TLR4, Toll-like receptor 4; TMA, trimethylamine; TMAO, trimethylamine-N-oxide; WAT, white adipose tissue.