The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity

Abstract

The interplay of gut microbiota, host metabolism, and metabolic health has gained increased attention. Gut microbiota may play a regulatory role in gastrointestinal health, substrate metabolism, and peripheral tissues including adipose tissue, skeletal muscle, liver, and pancreas via its metabolites short-chain fatty acids (SCFA). Animal and human data demonstrated that, in particular, acetate beneficially affects host energy and substrate metabolism via secretion of the gut hormones like glucagon-like peptide-1 and peptide YY, which, thereby, affects appetite, via a reduction in whole-body lipolysis, systemic pro-inflammatory cytokine levels, and via an increase in energy expenditure and fat oxidation. Thus, potential therapies to increase gut microbial fermentation and acetate production have been under vigorous scientific scrutiny. In this review, the relevance of the colonically and systemically most abundant SCFA acetate and its effects on the previously mentioned tissues will be discussed in relation to body weight control and glucose homeostasis. We discuss in detail the differential effects of oral acetate administration (vinegar intake), colonic acetate infusions, acetogenic fiber, and acetogenic probiotic administrations as approaches to combat obesity and comorbidities. Notably, human data are scarce, which highlights the necessity for further human research to investigate acetate’s role in host physiology, metabolic, and cardiovascular health.

Proteobacteria Overgrowth and Butyrate-Producing Taxa Depletion in the Gut Microbiota of Glycogen Storage Disease Type 1 Patients

“…The higher acetate concentration can be ascribed to several intestinal bacteria found to be more abundant in GSD gut microbiota, including Akkermansia muciniphila and Bifidobacterium spp., which produce acetate by fermenting acetogenic fibers, and to a lesser extent, protein-derived peptides [44].…”

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…Fat cells release leptin in higher concentration by the presence of acetate [223]. In a human study with thirty-four morbidly obese women and men through NMR analysis, increased plasma levels of acetate were found, with a positive correlation with gut Firmicutes, and negatively correlated with HOMA-IR and fasting TG [223,224]. In a study with NAFLD patients, acetate was found increased in circulatory level and fecal level, analyzed by NMR.…”

“…Firmicutes are positive related to acetate, thus when dysbiosis cause an increase of Firmicutes in obese rats, plasma acetate levels increase, and it is linked to insulin action in morbidly obese individuals through circulating acetate. Fat cells release leptin in higher concentration by the presence of acetate [223]. In a human study with thirty-four morbidly obese women and men through NMR analysis, increased plasma levels of acetate were found, with a positive correlation with gut Firmicutes, and negatively correlated with HOMA-IR and fasting TG [223,224].…”

“…Via cross-feeding mechanisms branched-chain and aromatic amino acids might be produced and further metabolized, altering gut integrity and impairing insulin sensitivity. That is to say gut-derived acetate production is determined by the balance in gut between saccharolytic and proteolytic fermentation which is determined by the presence of acetogenic fibers [223]. Firmicutes are positive related to acetate, thus when dysbiosis cause an increase of Firmicutes in obese rats, plasma acetate levels increase, and it is linked to insulin action in morbidly obese individuals through circulating acetate.…”

Distinct Microbial Assemblages Associated with Genetic Selection for High- and Low- Muscle Yield in Rainbow Trout

“…In humans, previous studies showed influence of gut microbiota in muscle fitness and degradation [13,14]. Symbiotic microbial population residing in humans supply short-chain fatty acids (SCFAs) to the skeletal muscle resulting in improved muscle percentage and fitness, whereas dysbiosis (imbalance in microbiota) results in muscle degradation in host due to increased intestinal permeability and liberation of endotoxin into circulation [14][15][16]. Muscle constitutes about 50-60% of the fish body weight [17] and plays a significant role in the regulation of nutrient metabolism, growth, and inflammation in humans as well as in fish [18][19][20].…”