Abstract | OBJECTIVE: 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:
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Authors | Shasha Zhang, Guangzhi Chen, Ning Li, Meiyan Dai, Chen Chen, Peihua Wang, Huiru Tang, Samantha L Hoopes, Darryl C Zeldin, Dao Wen Wang, Xizhen Xu |
Journal | Obesity (Silver Spring, Md.)
(Obesity (Silver Spring))
Vol. 23
Issue 7
Pg. 1401-13
(Jul 2015)
ISSN: 1930-739X [Electronic] United States |
PMID | 26053032
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 The Obesity Society. |
Chemical References |
- 14,15-dihydroxyeicosatrienoic acid
- Fatty Acids
- Fatty Acids, Nonesterified
- Triglycerides
- Cholesterol
- AMP-Activated Protein Kinases
- 8,11,14-Eicosatrienoic Acid
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Topics |
- 8,11,14-Eicosatrienoic Acid
(analogs & derivatives, metabolism)
- AMP-Activated Protein Kinases
(metabolism)
- Animals
- Cholesterol
(metabolism)
- Diet, High-Fat
- Disease Models, Animal
- Fatty Acids
(metabolism)
- Fatty Acids, Nonesterified
(metabolism)
- Hyperlipidemias
(metabolism)
- Lipid Metabolism
(drug effects)
- Liver
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Oxidative Stress
(drug effects)
- Triglycerides
(blood)
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