title: CYP2J2 overexpression ameliorates hyperlipidemia via increased fatty acid oxidation mediated by the AMPK pathway.
abstract: OBJECTIVE
  The study aims to investigate the effect of cytochrome P450 2J2 (CYP2J2) overexpression on hyperlipidemia in mice and further to explore its effect on fatty acid oxidation in vivo and in vitro.
  
  
  METHODS
  The effects and mechanisms of endothelial-specific CYP2J2 transgene (Tie2-CYP2J2-Tr) on lipid and fatty acid metabolism were investigated in high-fat diet (HFD) -treated mice. HepG2, LO2 cells, and HUVECs were exposed to 0.4 mM free fatty acid (FFA) for 24 h and used as a model to investigate the roles of CYP2J2 overexpression and epoxyeicosatrienoic acids (EETs) on fatty acid β-oxidation in vitro.
  
  
  RESULTS
  Tie2-CYP2J2-Tr mice had significantly lower plasma and liver triglycerides, lower liver cholesterol and fatty acids, and reduced HFD-induced lipid accumulation. CYP2J2 overexpression resulted in activation of the hepatic and endothelial AMPKα, increased ACC phosphorylation, and increased expression of CPT-1 and PPARα, which were all reduced by HFD treatment. In FFA-treated HepG2, LO2, and HUVECs, both CYP2J2 overexpression and EETs significantly decreased lipid accumulation and increased fatty acid oxidation via activating the AMPK and PPARα pathways.
  
  
  CONCLUSIONS
  Endothelial-specific CYP2J2 overexpression alleviates HFD-induced hyperlipidemia in vivo. CYP2J2 ameliorates FFA-induced dyslipidemia via increased fatty acid oxidation mediated by the AMPK and PPARα pathways.
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Peihua
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China.
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.affiliation: Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Hoopes
authors.affiliation: Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina, USA.
authors.forename: Darryl C
authors.initials: DC
authors.lastname: Zeldin
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Xizhen
authors.initials: X
authors.lastname: Xu
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
chemical_list: C107016:14,15-dihydroxyeicosatrienoic acid; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases; D015126:8,11,14-Eicosatrienoic Acid