Effects of walnut shell extract on lipid metabolism and serum metabolomics in rats with high-fat diet-induced obesity

• The study provided the theoretical basis for exploiting and utilizing walnut by-products. • To elucidate the effects of WSE on lipid metabolism and serum metabolome in HFD-induced obese rats. • The mechanism of WSE regulating lipid metabolism may be closely related to LEP, FAS, ADP, PPAR-γ and HSL. • The lipid-lowering effect of WSE was verified by serum metabolomics, and the expression of 29 potential biomarkers was reversed and returned to normal. Rich in flavonoids and phenolic compounds, walnut shells have lipid-lowering, antioxidant, and anti-inflammatory properties; however, their impact on blood lipids has not been widely documented. We investigated the effects of walnut shell extract (WSE) on the lipid metabolism and serum metabolomics of rats with obesity. The results showed that WSE reduced the body weight and serum TC、TG and LDL-c levels and increased the HDL-c levels in obese rats ( p < 0.05 ). It also decreased the activities of liver enzymes (ALT and AST), and modulated the levels of major lipid metabolism markers, downregulating LEP and FAS and upregulating ADP, PPAR-γ, and HSL. Additionally, serum metabolomic profiling was used to identify 29 differential metabolites, four of which were most significantly correlated with glycolipid metabolism. These results suggest that the potential mechanism of action of WSE in the treatment of hyperlipidemia is related to its regulatory effects on glycolipid metabolic pathways.