Gut Microbial-Derived Short Chain Fatty Acids: Impact on Adipose Tissue Physiology

Abstract

Obesity is a global public health issue and major risk factor for pathological conditions, including type 2 diabetes, dyslipidemia, coronary artery disease, hepatic steatosis, and certain types of cancer. These metabolic complications result from a combination of genetics and environmental influences, thus contributing to impact whole-body homeostasis. Mechanistic animal and human studies have indicated that an altered gut microbiota can mediate the development of obesity, leading to inflammation beyond the intestine. Moreover, prior research suggests an interaction between gut microbiota and peripheral organs such as adipose tissue via different signaling pathways; yet, to what degree and in exactly what ways this inter-organ crosstalk modulates obesity remains elusive. This review emphasizes the influence of circulating gut-derived short chain fatty acids (SCFAs) i.e., acetate, propionate, and butyrate, on adipose tissue metabolism in the scope of obesity, with an emphasis on adipocyte physiology in vitro and in vivo. Furthermore, we discuss some of the well-established mechanisms via which microbial SCFAs exert a role as a prominent host energy source, hence regulating overall energy balance and health. Collectively, exploring the mechanisms via which SCFAs impact adipose tissue metabolism appears to be a promising avenue to improve metabolic conditions related to obesity.

Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends

“…Short-chain fatty acids (SCFAs) are generated in the colon by the fermentation of dietary fiber by gut microbiota. Hepatocytes can utilize SCFAs as a source of energy, which can lower glucose production by the liver and enhance insulin sensitivity ( 39 , 40 ). SCFAs can also stimulate the secretion of intestinal hormones, including glucagon-like peptide-1 (GLP-1), which can further enhance insulin secretion and improve glucose metabolism ( 41 ).…”

Low Short-Chain-Fatty-Acid-Producing Activity of the Gut Microbiota Is Associated with Hypercholesterolemia and Liver Fibrosis in Patients with Metabolic-Associated (Non-Alcoholic) Fatty Liver Disease

“…Despite the increasing prevalence of MAFLD, the onset and progression of the disease remain unclear. This process probably depends on factors closely related to metabolic disorders, such as obesity, hypertension, dyslipidemia, and type 2 diabetes mellitus [1][2][3][4][5][6][7][8]. The main pathogenetic mechanisms of these diseases include inflammation, oxidative stress, insulin resistance, and dyslipidemia [3][4][5].…”

“…The first is the modulation of bile acid synthesis, which is critical for fat absorption and affects glucose metabolism through the farnesoid X receptor [8]. The second is the activation of the innate immune system due to the translocation of bacterial components [1][2][3][4][5][6]. The third is the production of endogenous ethanol [2,8]; reduced choline metabolism alters very low-density lipoprotein metabolism and promotes inflammation [3,4,7].…”

“…The third is the production of endogenous ethanol [2,8]; reduced choline metabolism alters very low-density lipoprotein metabolism and promotes inflammation [3,4,7]. Finally, there is a change in the production of short-chain fatty acids (SCFAs) [3][4][5][6][7][8][9].…”

“…It is well known that SCFAs, in addition to being the intestinal epithelium's energy supply, perform various biological functions, such as immunity regulation, lipogenesis, and gluconeogenesis [3,6,9,10]. Observations of variations in the levels of SCFAs in patients with MAFLD have been presented in the literature, but the results are highly contradictory.…”