Punicalagin Prevents Hepatic Steatosis through Improving Lipid Homeostasis and Inflammation in Liver and Adipose Tissue and Modulating Gut Microbiota in Western Diet‐Fed Mice

Scope Punicalagin (PU)‐rich pomegranate peel extract has been shown before to exert protective effects against high fat‐induced hepatic damage. The aim of this study is to explore whether and how PU antagonizes hepatic steatosis in Western diet‐fed (WD) mice. Methods and Results Mice are fed either chow diet, WD (containing 42% fat, 15% protein, and 43% carbohydrates), or WD supplemented with PU (50 mg kg −1 body weight/day) for 13 weeks. Weight gain, hepatic fat content, and inflammation in the liver and adipose tissues are measured. Compared to the WD group, PU‐treated mice have lower fat content, decreased levels of alanine transaminase, and inflammation in liver. PU also changed the transcriptional expression of important genes in fatty acid oxidation pathway and alleviated glucose intolerance. Furthermore, PU improved adiponectin signaling and lipid metabolism in visceral adipose tissue. Moreover, PU improved gut microbiota dysbiosis induced by WD and enhanced gut barrier function. Conclusions The findings suggest that PU improves hepatic steatosis induced by WD, in part through regulating lipid homeostasis and inflammation in liver and adipose tissue and restoring microbiota shift and impaired gut barrier function. Thus, PU can be potentially developed as a potential prevention strategy in combating nonalcoholic fatty liver disease.