Modulation of Adipocyte Metabolism by Microbial Short-Chain Fatty Acids

Abstract

Obesity and its complications—including type 2 diabetes, cardiovascular disease, and certain cancers—constitute a rising global epidemic that has imposed a substantial burden on health and healthcare systems over the years. It is becoming increasingly clear that there is a link between obesity and the gut microbiota. Gut dysbiosis, characterized as microbial imbalance, has been consistently associated with obesity in both humans and animal models, and can be reversed with weight loss. Emerging evidence has shown that microbial-derived metabolites such as short-chain fatty acids (SCFAs)—including acetate, propionate, and butyrate—provide benefits to the host by impacting organs beyond the gut, including adipose tissue. In this review, we summarize what is currently known regarding the specific mechanisms that link gut-microbial-derived SCFAs with adipose tissue metabolism, such as adipogenesis, lipolysis, and inflammation. In addition, we explore indirect mechanisms by which SCFAs can modulate adipose tissue metabolism, such as via perturbation of gut hormones, as well as signaling to the brain and the liver. Understanding how the modulation of gut microbial metabolites such as SCFAs can impact adipose tissue function could lead to novel therapeutic strategies for the prevention and treatment of obesity.

Quinoa Reduces High-Fat Diet-Induced Obesity in Mice via Potential Microbiota-Gut-Brain-Liver Interaction Mechanisms

“…GLP-1 is released after food intake and acts to amplify glucose-dependent insulin secretion, and it has been in the spotlight as a target for the treatment of obesity and diabetes as its positive effects on glucose homeostasis, appetite regulation, gastric emptying and postprandial lipid metabolism ( 26 , 27 ). In addition to TGR5, short-chain fatty acids (SCFAs), metabolites of intestinal microbiota, can promote GLP-1 secretion from L cells and improve glucose tolerance ( 28 ). Among them, butyrate is a major metabolite that can stimulates secretion of GLP-1 to augment the insulin, while probiotics, represented by Akkermansia , increase circulating butyrate ( 29 ).…”

Why Do These Microbes Like Me and How Could There Be a Link with Cardiovascular Risk Factors?

“…Among them, propionate and butyrate seem to play the most significant health-promoting roles [125]. SCFAs are absorbed by diffusion or via GPR41 and GPR43 in the intestine [126]. A normal colonic epithelium derives 60-70% of its energy supply from SCFA-butyrate [127].…”

“…Propionate is transported to the liver and used as a precursor for gluconeogenesis, liponeogenesis, and protein synthesis [128], while acetate can be used as a substrate for lipogenesis and gluconeogenesis [125,129]. SCFAs may also target the liver to reduce hepatic glucose production and lipid accumulation via AMPK activation [126]. SCFAs can directly signal to adipose tissue via GPR43/GPR41 and enhance adipogenesis and uncoupling protein-1 production while restraining lipolysis and inflammation [126].…”

“…SCFAs may also target the liver to reduce hepatic glucose production and lipid accumulation via AMPK activation [126]. SCFAs can directly signal to adipose tissue via GPR43/GPR41 and enhance adipogenesis and uncoupling protein-1 production while restraining lipolysis and inflammation [126]. Furthermore, SCFA might target the brain via GPR41 and also stimulate the production of satiety hormones (glucagon-like peptide 1 and protein YY) production [126].…”

“…SCFAs can directly signal to adipose tissue via GPR43/GPR41 and enhance adipogenesis and uncoupling protein-1 production while restraining lipolysis and inflammation [126]. Furthermore, SCFA might target the brain via GPR41 and also stimulate the production of satiety hormones (glucagon-like peptide 1 and protein YY) production [126]. In the study of Frost G. et al, acetate was shown to accumulate in the hypothalamus and induce acetyl-coenzyme carboxylase activation A, causing a change in the expression profile of regulatory neuropeptides and leading to appetite suppression [130].…”