1655-P: GLP-1R Is Required for Resveratrol in Exerting Its Metabolic Beneficial Effect in HFD-Challenged Male Mice

The beneficial effects of dietary polyphenols including resveratrol have been elucidated during the past 2-3 decades, yet the mechanism underlying their metabolic functions remains elusive or even controversial. Recent investigations revealed that hepatic hormone FGF21 is the common target for both GLP-1RAs and dietary polyphenol intervention. Here we utilized wild type (WT) and GLP-1R^-/- mice to access whether GLP-1R is required for resveratrol to exert its beneficial effects. In WT male mice with HFD challenge, concomitant resveratrol intervention (REV-I) for 12 weeks reduced body weight gain and improved glucose tolerance, while in male GLP-1R^-/- mice, such metabolic effects were lost. In WT mouse liver and epididymal white adipose tissue (eWAT), REV-I ameliorated HFD-induced FGF21 resistant and stimulated a battery of genes that are involved in lipid homeostasis. In addition, HFD-induced alterations on expressions of a battery of adipose tissue specific genes including those encode for leptin and adiponectin were reversed by concomitant REV-I. REV-I was also shown to exert anti-inflammatory effects in the ileum of WT mice fed with HFD. Specifically, genes that encode for a battery of pro-inflammatory markers including IL-1β and IFN-γ were significantly elevated by HFD challenge, while REV-I attenuated their expression. HFD challenge also reduced IL-10 mRNA level in the WT mouse ileum, while REV-I restored the expression. Together, we bring a novel player GLP-1R to explore the mechanism underlying the metabolic functions of resveratrol. Collectively, we conclude that the metabolic beneficial effects of resveratrol on reducing body weight gain and improving glucose disposal require GLP-1R.