Sea buckthorn pulp oil modulates MAFLD through lipid reprogramming and inflammatory resolution: insights from integrated omics analysis.

Metabolic dysfunction-associated fatty liver disease (MAFLD), the most prevalent chronic liver disorder, can progress to hepatic fibrosis and directly determine patients' long-term prognosis. Sea buckthorn pulp oil (SBO) is rich in bioactive lipids, yet its lipid profile and potential mechanisms underlying its amelioration of MAFLD-related liver injury remain elusive. Targeted lipidomics identified abundant palmitoleic acid-containing lipids in SBO, which significantly alleviated inflammation, hepatic steatosis, and glucose dysregulation, and inhibited abnormal collagen deposition and α-SMA expression in MAFLD mice. Integrated analysis of untargeted metabolomics, transcriptomics, and targeted lipidomics confirmed that SBO could remodel lipid metabolism, inhibit the TLR4/AP-1 axis, reduce immune infiltration, and modulate the M1/M2 imbalance; simultaneously, it significantly upregulated the levels of specialized pro-resolving lipid mediators (SPMs) and their intermediates, particularly 12-HEPE and 17(S)-HDHA. These results demonstrate that SBO may ameliorate aberrant activation of macrophages, neutrophils, and hepatic stellate cells by downregulating the TLR4/AP-1 pathway and promoting SPM-related inflammatory resolution, thereby ameliorating MAFLD-related hepatic injury.