Exogenous butyrate regulates lipid metabolism through GPR41-ERK-AMPK pathway in rabbits

Abstract

Diets containing higher levels of fat can lead to obesity, which is potentially harmful to health. Endogenous butyric acid is produced by intestinal microbial fermentation and participates in lipid metabolism. However, there is less butyric acid produced in the body, butyric acid has a shorter half-life in the blood. We used intraperitoneal injection of sodium butyrate to study the mechanism of butyrate involved in body lipid metabolism. Triglycerides in adipose tissue and liver were significantly reduced by butyrate. The content of triglyceride in plasma in butyrate group was also significantly decreased. In adipose tissue, butyrate up-regulated gene expression of hormone-sensitive lipase (HSL), carnitine palmitoyl transferase (CPT)1 and CPT2, and increased protein expression of G protein-coupled receptor (GPR)41, phosphorylated extracellular-signal-regulated kinase (P-ERK), adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and P-AMPK. Gene expression of lipoprotein lipase (LPL), differentiation-dependent factor 1 (ADD1) and fatty acid synthase (FAS) was down-regulated. In liver, butyrate up-regulated protein expression of GPR41, ERK, P-ERK, P-AMPK. Gene expression of ADD1 and FAS was down-regulated. In muscle tissue, butyrate significantly up-regulated the expression of gene LPL, fatty acid transport protein (FATP) and fatty acid-binding protein (FABP) and protein GPR41, GPR43. Thus, butyrate is involved in body lipid metabolism mainly through the GPR41-mediated ERK-AMPK pathway. Inhibits lipid synthesis in adipose tissue and the liver and promotes lipolysis, avoiding obesity caused by diets with higher fat content. Highlights Butyrate affects lipid metabolism in the body by affecting lipid synthesis/decomposition in adipose tissue and liver. Butyrate mainly through GPR41-mediated ERK-AMPK pathway, inhibit lipid synthesis, promote lipid decomposition, and avoid a large amount of fat accumulation induced by higher-fat diet.