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.
Highlights
Obesity has reached pandemic proportions worldwide, and its increased prevalence is associated with a plethora of metabolic disturbances [1]
The obese state is characterized by increased adipose tissue mass and disturbed function resulting in systemic lipid spillover and low-grade inflammation, which may contribute to the development of comorbidities such as type 2 diabetes mellitus (T2DM)
We focus on the metabolic effects of the most abundant gut-derived metabolite, known as acetate, which may improve the obese insulin resistant state through various effects in peripheral tissues that collectively improve body weight control and insulin sensitivity
Summary
Obesity has reached pandemic proportions worldwide, and its increased prevalence is associated with a plethora of metabolic disturbances [1]. (FFAR3), which are expressed at the mRNA and protein level in the human colon [23,24] but are expressed in the small intestine, such as, in particular, the ileum [25] These receptors have been shown to be expressed at the mRNA level in various insulin sensitive tissues such as the adipose tissue [26], skeletal muscle, liver [27], and pancreatic beta cells [28,29], which illustrates their broad metabolic role. Acetate may be converted to acetyl-CoA and incorporated in the tricarboxylic acid (TCA) cycle in various peripheral tissues [30,31,32] It may impact metabolism through increments in oxidative capacity (e.g., liver and skeletal muscle) via effects on 50 AMP-activated protein kinase (AMPK) phosphorylation [33,34,35]. We discuss potential therapeutic approaches to improve insulin sensitivity and metabolic health, including oral acetate administration (vinegar intake), acetogenic fiber, and probiotic supplementations
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