Short-Chain Fatty Acid Acetate Stimulates Adipogenesis and Mitochondrial Biogenesis via GPR43 in Brown Adipocytes

Abstract

Short-chain fatty acids play crucial roles in a range of physiological functions. However, the effects of short-chain fatty acids on brown adipose tissue have not been fully investigated. We examined the role of acetate, a short-chain fatty acid formed by fermentation in the gut, in the regulation of brown adipocyte metabolism. Our results show that acetate up-regulates adipocyte protein 2, peroxisomal proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 expression and affects the morphological changes of brown adipocytes during adipogenesis. Moreover, an increase in mitochondrial biogenesis was observed after acetate treatment. Acetate also elicited the activation of ERK and cAMP response element-binding protein, and these responses were sensitive to G(i/o)-type G protein inactivator, Gβγ-subunit inhibitor, phospholipase C inhibitor, and MAPK kinase inhibitor, indicating a role for the G(i/o)βγ/phospholipase C/protein kinase C/MAPK kinase signaling pathway in these responses. These effects of acetate were mimicked by treatment with 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide, a synthetic G protein-coupled receptor 43 (GPR43) agonist and were impaired in GPR43 knockdown cells. Taken together, our results indicate that acetate may have important physiological roles in brown adipocytes through the activation of GPR43.

Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice

“…BAT activity was also slightly increased in inulin- and HAc-supplemented mice, which is in accordance with recent literature data 11 . Sahuri-Arisoylu et al .…”

“…While propionate is primarily a precursor for (intestinal) gluconeogenesis 6, 7 and an inhibitor of hepatic lipid synthesis 8 , acetate was also shown to increase energy expenditure by activating AMP-activated protein kinase (AMPK) in liver and muscle 9, 10 . Furthermore, recent literature data claim that acetate increases the activity of brown fat and induces the formation of “beige adipocytes” 11–13 .…”

Dietary grape seed proanthocyanidins (GSPs) improve weaned intestinal microbiota and mucosal barrier using a piglet model

“…On contrast, the expression of GPR43 and GPR109A had no difference in different groups, which suggest that GPR41 may play an role important role in the GSPs treatment. Our findings are consistent with the previous studies, which indicated that GPR41 gene is highly expressed in intestinal tissue and adipose tissue, while GPR43 gene is highly expressed in the hypothalamus and adipose tissue [38]. GPR109A is mainly expressed in adipose tissue, spleen and immune cells [39].…”

Gut Microbiota Interacts with Markers of Adipose Tissue Browning, Insulin Action and Plasma Acetate in Morbid Obesity

“…To explore the possible mechanism underlying the relationship between microbiota and adipose tissue browning, and considering the effects of circulating acetate on adipocyte browning and fat oxidation, its major abundance compared to other important gut microbial‐derived short‐chain fatty acids (propionate and butyrate), and its capacity to transfer from colon into bloodstream, circulating acetate levels in plasma were examined. Circulating acetate levels were significantly increased in insulin sensitive obese participants ( Figure a, Table ) in positive correlation with gut Firmicutes RA, SAT PRDM16 mRNA, and insulin sensitivity (Figure b–d), and negatively correlated with HOMA‐IR and fasting triglycerides (Figure e, f).…”