Cheonggukjang Attenuates Lipid Dysmetabolism by Modulating Gut Microbiota-Derived SCFA Production and G-Protein-Coupled Receptor Levels in White Adipose Tissue.

Cheonggukjang (CGJ) exerts anti-obesity and lipid-lowering effects; however, its effects on gut microbiota-derived short-chain fatty acid (SCFA) production, adipose G protein-coupled receptor (GPCR) expression, and the mechanistic associations between them have not been investigated. Thus, the current study aimed to investigate these relationships in relation to lipid metabolism in white adipose tissue (WAT). Two distinct CGJ samples were administered to high-fat/high-cholesterol diet-induced (HCFD) obese mice. CGJ slightly lowered body weight gain and significantly improved dyslipidemia and hepatic lipid accumulation, also improving WAT lipid metabolism-related gene expression. Additionally, CGJ reversed gut microbiota dysbiosis, increased the abundance of genera associated with SCFA production, and increased colonic SCFA levels. Adipose Gpr41 and Gpr109a expressions were upregulated, and their mRNA levels were strongly correlated with systemic lipid indicators and WAT lipid-metabolism genes. To the best of our knowledge, this is the first study to provide evidence that CGJ modulates gut microbiota-derived SCFA levels and elevates adipose GPCR gene expression, suggesting that CGJ may exert anti-obesity and lipid-metabolism-alleviating effects through the gut microbiota-SCFA-adipose GPCR-WAT lipid metabolism axis.