Dietary milk polar lipids ameliorate hepatic lipid accumulation through coordinated regulation of Wnt-PPARγ signaling and remodeling of the gut microbiota.

This study investigated the protective effects of milk polar lipids (MPL) against non-alcoholic fatty liver disease (NAFLD) and explored the underlying mechanisms using a high-fat high-sucrose (HFHS) diet-induced mouse model. MPL diet significantly reduced body weight gain, adiposity, and hepatic lipid accumulation, in addition to decreasing serum levels of liver injury markers. Mechanistically, MPL diet activated hepatic Wnt/β-catenin signaling, as evidenced by increased expression of low-density lipoprotein receptor-related protein 6 (LRP6), Wnt family member 3 A (Wnt3a), and β-catenin. Concurrently, MPL treatment suppressed peroxisome proliferator-activated receptor gamma (PPARγ) and downstream lipogenic proteins involved in triglyceride synthesis and de novo lipogenesis. In addition, MPL diet markedly reshaped the gut microbiota composition disrupted by HFHS feeding. Notably, MPL group showed a significant increased the abundance of Akkermansia muciniphila and short-chain fatty acid-producing bacteria, including members of Romboutsia and Christensenellaceae. These findings demonstrate that dietary MPL effectively attenuates HFHS diet-induced NAFLD through coordinated regulation of hepatic Wnt-PPARγ signaling and gut microbial ecology.