Shasha Zhang1, Guangzhi Chen1, Ning Li2, Meiyan Dai1, Chen Chen1, Peihua Wang1, Huiru Tang2, Samantha L Hoopes3, Darryl C Zeldin3, Dao Wen Wang1, Xizhen Xu1. 1. Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. 2. 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. 3. Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina, USA.
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.
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: Shilin Yang; Li Lin; Ji-Xiong Chen; Craig R Lee; John M Seubert; Yan Wang; Hong Wang; Zhong-Ren Chao; De-Ding Tao; Jian-Ping Gong; Zai-Ying Lu; Dao Wen Wang; Darryl C Zeldin Journal: Am J Physiol Heart Circ Physiol Date: 2007-02-23 Impact factor: 4.733
Authors: Nader G Abraham; Komal Sodhi; Anne M Silvis; Luca Vanella; Gaia Favero; Rita Rezzani; Craig Lee; Darryl C Zeldin; Michal L Schwartzman Journal: Hypertension Date: 2014-09-22 Impact factor: 10.190
Authors: Nicole S Carlson; Jennifer K Frediani; Elizabeth J Corwin; Anne Dunlop; Dean Jones Journal: Biol Res Nurs Date: 2020-01-27 Impact factor: 2.522
Authors: Maayan Waldman; Lars Bellner; Luca Vanella; Joseph Schragenheim; Komal Sodhi; Shailendra P Singh; Daohong Lin; Anand Lakhkar; Jiangwei Li; Edith Hochhauser; Michael Arad; Zbigniew Darzynkiewicz; Atallah Kappas; Nader G Abraham Journal: Stem Cells Dev Date: 2016-06-27 Impact factor: 3.272