Loganin regulates glycolipid metabolism by influencing intestinal microbiota and AMPK signaling in obese mice

Objective: We aimed to observe the effects of loganin (Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase (AMPK) signaling in obese mice. Methods: A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research (ICR) mice. Body weight was measured weekly and fasting blood glucose (FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol (TC), triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), and free fatty acids (FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing. Results: Log significantly decreased the body weight and the FBG in obese mice (P < .05), and it could restore FBG to normal levels. The total cholesterol, LDL-C, and FFA levels were significantly reduced by Log compared with the obese controls (TC: P = .0020; LDL-C: P = .0233; FFA: P = .0127), and the glucose tolerance of animals was significantly improved (P = .0477). The western blot results showed that Log could upregulate the protein expression of Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPKα), Sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor-gamma coactivator -1alpha (PGC1α) in skeletal muscle tissue of obese mice. 16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice. Conclusions: Log was effective in reducing body weight and improving glucolipid metabolism in obese mice, probably through activating AMPK signaling and regulating intestinal microbial diversity.