@article{Chen2025, 
author = {Yan-fang Chen and Ze-kai Fan and Yin-peng Wang and Peng Liu and Yi-xuan Cong and Yuan Wang and Ting Zhao and Tong-cheng Xu and Andrew J Sinclair and Duo Li and Xiao-fei Guo},
title = {Marine n-3 Polyunsaturated Fatty Acids Alleviate Metabolic Dysfunction-Associated Fatty Liver Disease Through Adiponectin-Ceramide Axis},
year = {2025},
journal = {Food Science and Human Wellness},
keywords = {Docosahexaenoic acid, Ceramide, Adiponectin, Eicosapentaenoic acid, n-3 polyunsaturated fatty acids, Metabolic dysfunction-associated fatty liver disease},
url = {https://www.sciopen.com/article/10.26599/FSHW.2025.9250806},
doi = {10.26599/FSHW.2025.9250806},
abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized as hepatic triglyceride accumulation, affects a quarter of the adult population worldwide, but limited therapeutic approaches are available in the treatment of MAFLD. It is widely believed that marine n-3 polyunsaturated fatty acids (PUFA) intervention could ameliorate MAFLD, however, the underlying mechanism remains elusive. Herein, in a case-control study, we identified serum C16:0-ceramide as a biomarker indicating MAFLD patients, which was negatively associated with n-3 PUFA levels in red blood cell phospholipids. The causality was confirmed by a randomized controlled trial (RCT), highlighting that supplemental n-3 PUFA had notable action in lowering serum C16:0-ceramide concentrations. The RCT indicated that serum adiponectin levels were negatively associated with serum C16:0-ceramide levels. An MAFLD model was established in mice fed a high-fat, high-cholesterol diet, and administration of n-3 PUFA increased adiponectin secretion and decreased hepatic C16:0-ceramide concentrations associated with reduced hepatic steatosis. In these mice, adiponectin administration contributed to decreased hepatic C16:0-ceramide concentrations and alleviated hepatic triglyceride accumulation through reduced de novo fatty acid synthesis and increased fatty acid β-oxidation. Furthermore, administration of C16:0-ceramide reversed the beneficial effects of n-3 PUFA in high-fat diet-induced MAFLD. This work reveals a novel mechanism, namely adiponectin-C16:0-ceramide axis, through which n-3 PUFA play a notable role in ameliorating MAFLD.}
}