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.

Keywords: acetate; dietary fiber; microbiota; obesity; type 2 diabetes.

Figure 1

Acetate sources and acetate-mediated effects in metabolic health. Exogenous acetate production includes vinegar as well as the supplementation of acetogenic fiber and probiotics. Acetogenic fiber characteristics (e.g. length, glycosidic bond configuration) may determine acetate production. Endogenous acetate production occurs in all tissues but predominantly in the liver. Microbial acetate is mainly produced in the colon. Colonic absorption and acetate systemic concentrations may differ between colonic production sites (proximal/distal). Importantly, acetate may increase GLP-1 and PYY secretion in the colon. Systemic acetate may improve metabolic health via improvements in adipose tissue functioning (antilipolytic/anti-inflammatory effects) insulin sensitivity and oxidative capacity (e.g. liver, skeletal muscle) increments in satiety (central nervous system) and modulation of insulin secretion (pancreas). Solid lines indicate well-studied effects of acetate, dashed line indicate more inconsistent findings.