Journal Article Epublish 8 citations
PubMed: 40052160 DOI: 10.34133/research.0577
Fat-1 Ameliorates Metabolic Dysfunction-Associated Fatty Liver Disease and Atherosclerosis through Promoting the Nuclear Localization of PPARα in Hamsters.
Research (Wash D C) 8:0577
Authors: Wenxi Zhang, Jiabao Guo, Guolin Miao, Jingxuan Chen, Yitong Xu, Pingping Lai, Lianxin Zhang, Yufei Han, Sin Man Lam, Guanghou Shui, Yuhui Wang, Wei Huang, Xunde Xian
Affiliations
- Institute of Cardiovascular Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. LipidALL Technologies Company Limited, Changzhou 213022, Jiangsu Province, China.
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
- Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University Third Hospital, Beijing 100191, China.
Abstract
Fat-1, an enzyme encoded by the gene, is responsible for the conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 polyunsaturated fatty acids in . To better investigate whether the expression of Fat-1 will exert a beneficial function in dyslipidemia and metabolic dysfunction-associated fatty liver disease (MAFLD), we established an adeno-associated virus 9 expressing Fat-1. We found that adeno-associated-virus-mediated expression of Fat-1 markedly reduced the levels of plasma triglycerides and total cholesterol but increased high-density lipoprotein levels in male wild-type hamsters on both chow diet and high-fat diet as well as in chow-diet-fed male LDLR hamsters. Fat-1 ameliorated diet-induced MAFLD in wild-type hamsters by enhancing fatty acid oxidation through the hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent pathway. Mechanistically, Fat-1 increased the levels of multiple lipid derivatives as ligands for PPARα and simultaneously facilitated the nuclear localization of PPARα. Our results provide new insights into the multiple therapeutic potentials of Fat-1 to treat dyslipidemia, MAFLD, and atherosclerosis.
MeSH
Liver Diseases, Non-Alcoholic Fatty Liver Disease, Dyslipidemias, Liver, Diet, Viruses, Atherosclerosis, Fatty Liver, Fatty Acids