Curcumin Compensates GLP-1 Deficiency via the Microbiota-Bile Acids Axis and Modulation in Functional Crosstalk between TGR5 and FXR in ob/ob Mice

Scope: Glucagon-like peptide-1 (GLP-1) deficiency occurs in obesity-related pathologies due to defects in the intestinal lumen. And expanding the L-cell population has emerged as a promising avenue to elevate GLP-1 secretion to tackle metabolic disorders. Curcumin (Cur), the principal active component of spice turmeric, possesses well-established anti-obesity properties. To clarify, the study investigates whether Cur promotes GLP-1 secretion built upon the L-cell expansion. Methods and results: Cur (60 mg kg(-1)) is administered orally to male ob/ob mice for 8 weeks. Cur ameliorates obesity and impaires glucose tolerance through increasing energy expenditure in ob/ob mice, accompanied by the maintenance of crypt architecture and gut permeability. It refines the microbial structure and bile acid (BA) profiles, resulting in deoxycholic acid (DCA) accumulation by weakening the enrichment of Lactobacillus. Further analyses show radically different properties of Cur on the intestine function of TGR5 and FXR (i.e., activation and repression). Cur amplifies L-cell number to promote GLP-1 secretion in ob/ob mice. Conclusions: The findings suggest that Cur may act as a natural TGR5 agonist and FXR antagonist to improve obesity by enhancing GLP-1 release from L-cell expansion via the gut microbiota-BAs-TGR5/FXR axis, and it may serve as a promising therapeutic agent to compensate obesity-related metabolic disorders.

Automated summary

This study suggests that curcumin may act as a natural agonist of TGR5 and an antagonist of FXR to improve obesity by promoting GLP-1 secretion through expanding L-cell population via the gut microbiota-bile acids-TGR5/FXR axis. It may serve as a promising therapeutic agent for obesity-related metabolic disorders.