The Ameliorative Effect and Mechanisms of Ruditapes philippinarum Bioactive Peptides on Obesity and Hyperlipidemia Induced by a High-Fat Diet in Mice

In this study, bioactive peptides (RBPs) from Ruditapes philippinarum were prepared by fermentation with Bacillus natto and the effect and mechanisms of RBPs on obesity and hyperlipidemia were explored in mice. We found that RBPs significantly reduced body weight, adipose tissue weight, accumulation of hepatic lipids, and serum levels of total cholesterol (CHO), triglyceride (TG), and low-density lipoprotein (LDL). Mechanistic studies showed that RBPs up-regulated the hepatic expression of genes related to lipolysis, such as hormone-sensitive lipase (HSL), phosphorylated AMP-activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptors α (PPARα), and down-regulated the expression of peroxisome proliferator-activated receptors γ (PPARγ) which is related to lipid synthesis. In addition, RBPs could attenuate obesity and hyperlipidemia by regulating disordered gut microbiota composition, such as increasing the abundance of microflora related to the synthesis of short chain fatty acids (SCFAs) (Bacteroidetes, Prevotellaceas_UCG_001, norank_f_Muribaculaceae, and Odoribacter) and controlling those related to intestinal inflammation (reduced abundance of Deferribacteres and increased abundance of Alistipes and ASF356) to exert anti-obesity and lipid-lowering activities. Our findings laid the foundation for the development and utilization of RBPs as a functional food to ameliorate obesity and hyperlipidemia.