Brown adipose tissue-derived Nrg4 alleviates non-alcoholic fatty liver disease in mice

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, seriously affecting human health. Carnosine, which widely exists in the skeletal muscle of marine migratory fish, birds, and chickens, is a non-protein histidine dipeptide with anti-inflammatory properties. To investigate whether carnosine can alleviate high-fat diet (HFD)-induced NAFLD. Mice were fed a HFD and orally administered with carnosine at doses of 60, 120, and 240 mg/kg/day for 16 weeks. Its lipid content, liver oxidative damage, neuregulin 4 (Nrg4), lipid-associated protein, and inflammation-related protein content in mice were measured and its brown fat morphology were observed by microscope. Results showed that carnosine significantly inhibited mice body weight gain (reduced by 28.90%, 25.43%, and 42.34%, respectively), liver oxidative damage, and lipid metabolism and decreased its serum interleukin-1β (IL-1β) content in HFD-induced obese mice (P < 0.05). Western blot analysis showed that carnosine could activate brown adipose tissue and upregulate Nrg4 to inhibit sterol regulatory element binding protein-1 (SREBP-1) expression and the NOD-like receptor thermal protein domain associated protein 3/ nuclear factor kappa-B (NLRP3/NF-κB) pathway. These results indicated that carnosine could lessen the effects of a HFD on NAFLD in mice.