Sodium acetate, propionate, and butyrate reduce fat accumulation in mice via modulating appetite and relevant genes

Objectives: Acetate, propionate, and butyrate, three of the most common short-chain fatty acids (SCFAs), can be produced when some non-digestible carbohydrates enter the large intestine and undergo bacterial fermentation. The aim of this study was to investigate the effects of these three SCFAs on appetite regulation and lipid metabolism and to determine the extent that appetite contributes to the beneficial influences of SCFAs. Methods: In a 35-d study, 48 C57BL/6J male mice were randomly allocated to six groups: control; 5% sodium acetate; 5% sodium propionate; 5% sodium butyrate; pair fed 1; and pair fed 2. Results: The study showed that dietary supplementation of sodium acetate reduced serum triacylglycerol, free fatty acids, glucose, and interleukin (IL)-6 levels (P < 0.05), increased serum glucagon-like peptide 1, and leptin levels (P < 0.05), downregulated the mRNA expressions of fatty acid synthase, peroxisome proliferator-activated receptor, and lipoprotein lipase (P < 0.05), and upregulated the mRNA expressions of fasting induced adipose factor, nuclear respiratory factor 1, mitochondrial transcription factor A, tumor necrosis factor receptor superfamily member 9, cytochrome-C oxidase IV and free fatty acid receptor 2 (P < 0.05). Sodium propionate also reduced serum IL-1 beta level (P < 0.05), increased serum peptide YY level (P < 0.05), downregulated the mRNA expressions of acetyl-coenzyme A carboxylase and sterol regulatory element binding protein 1c (P < 0.05), and upregulated the mRNA expression of transmembrane protein 26 (P < 0.05). Additionally, sodium butyrate decreased average daily feed intake (P < 0.05) downregulated the mRNA expression of myosin heavy-chain (MyHc) IIb (P < 0.05), and upregulated the mRNA expressions of lipase hormone-sensitive, MyHC IIa and carnitine palmitoyltransferase-1 alpha(P < 0.05). Moreover, the metabolic benefits of SCFAs were partly attributed to the reduction of feed intake. Conclusion: Taken together, SCFAs could reduce appetite and fat accumulation via modulating relevant genes and hormones, which might further illustrate the potential mechanisms that underlay the effects of SCFAs on lipid homeostasis and control of body weight. (C) 2021 Elsevier Inc. All rights reserved.