Modulation of lipid profile by flaxseed cyclolinopeptides ameliorates lipid accumulation in obese mice liver and pancreas

Flaxseed cyclolinopeptides (CLs) inhibit the lipid oxidation during in vitro digestion of high-fat meat. However, the effect of CLs on high-fat diet (HFD) induced lipid impairment metabolism remains unclear. Therefore, this study aimed to investigate the impact of CLs on HFD-induced lipid metabolism in the liver and pancreas of mice. The results demonstrated that the CLs administration significantly improved serum lipids (TG, TC, and LDL-C) in the HFD-induced model ( p < 0.05). Histological analysis using H&E and immunofluorescence staining revealed that CLs significantly restored pancreatic structure, and enhanced the secretion of insulin and glucagon. Furthermore, CLs intervention significantly improved antioxidant capacity in both the liver and pancrease by increasing the level of GSH-Px, T-GSH and GSH while decreasing GSSG and MDA levels in HFD-induced model. Lipidomic analysis further revealed that CLs treatment significantly reduced the levels of several lipid metabolites, including lysophosphatidylcholines (LPC), phosphatidylinositols (PI), lysophosphatidylethanolamines (LPE), phosphatidylethanolamines (PE), fatty acyls (FA), and diacylglycerols (DG), while increasing the levels of sphingomyelins (SM) and phosphatidylcholines (PC) compared to the model group. Pathway enrichment analysis indicated that CLs promoted the fatty acids metabolism and biosynthesis of unsaturated fatty acid, as supported by the upregulated expression of lipid metabolism gene/protien (CPT1, SLC7A11 and GPX4) and downregulated expression of lipid tranporter gene/protien (CD36, ACSL4, LPCAT3, and P35). Collectively, these findings suggest that CLs effectively enhance hepatic and pancreatic functiona and inhibit lipid accumulation in liver and pancreas through modulation of the CD36/p53/ACSL4 signalling pathway.