5‐Heptadecylresorcinol ameliorates high‐fat diet induced non‐alcoholic fatty liver disease through modulating bile acid profile and suppressing inflammation

Abstract BACKGROUND The risk of non‐alcoholic fatty liver disease (NAFLD) has been inversely associated with whole grain consumption. 5‐Heptadecylresorcinol (AR‐C17) is a phenolic lipid present in the bran part of whole grain wheat, which has been proven to ameliorate obesity and atherosclerosis. However, whether AR‐C17 could alleviate NAFLD and the underlying molecular mechanisms remain unclear. RESULTS AR‐C17 administration (150 mg/kg) significantly attenuated high‐fat diet (HFD)‐induced NAFLD in mice by reducing serum total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), and aspartate aminotransferase (AST) levels, accompanied by significant improvements in hepatic steatosis, inflammation, and fibrosis. Accordingly, serum metabolomics revealed distinct clustering of different treatment groups, and the pathway enrichment analyses indicated that AR‐C17 could significantly modulate primary bile acid biosynthesis. Hepatic target metabolomics further confirmed that AR‐C17 administration profoundly altered bile acid profiles. Western‐blot analysis showed that AR‐C17 treatment up‐regulated FXR (farnesoid X receptor) expression and inhibited the activation of NLRP3 (nucleotide‐binding oligomerization domain‐like receptor with a pyrin domain 3) inflammasome. CONCLUSION AR‐C17 mitigated the progression of NAFLD by modulating the hepatic bile acid profile and reducing systemic inflammation through FXR signaling pathway. © 2025 Society of Chemical Industry.