title: CYP2J3 gene delivery up-regulated adiponectin expression via reduced endoplasmic reticulum stress in adipocytes.
abstract: Ample evidences demonstrate that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play crucial and diverse roles in cardiovascular homeostasis. We and others have identified that EETs exert a beneficial role on insulin resistance and diabetes. This study investigated the effects of CYP2J3 epoxygenase gene delivery on adiponectin expression in rats treated with high-fat (HF) diet. CYP2J3 gene delivery in vivo increased EET generation, enhanced adiponectin expression and secretion and accompanied by activation of adiponectin downstream signaling, and decreased insulin resistance as determined by plasma insulin levels, insulin resistance index and glucose tolerance test, as well as phosphorylation of protein kinase B in both liver and muscle. Furthermore, CYP2J3 overexpression prevented HF diet-induced endoplasmic reticulum (ER) stress in adipose tissue of rats. Also, CYP2J3 gene transfection and exogenous administration of EETs inhibited thapsigargin-induced ER stress with increased adiponectin expression and secretion in differentiated 3T3-L1 adipocytes. Thus, CYP2J3 gene delivery up-regulated adiponectin expression and excretion in adipose tissue of rats treated with HF diet through inhibition of ER stress, which can decrease adiponectin expression. These results further highlight the beneficial roles of the CYP epoxygenase 2J3 and its metabolites EETs on adiponectin expression and secretion.
authors.affiliation: Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Xizhen
authors.initials: X
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Tu
authors.forename: Wenjing
authors.initials: W
authors.lastname: Feng
authors.forename: Ben
authors.initials: B
authors.lastname: Ma
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Changlong
authors.initials: C
authors.lastname: Zheng
authors.forename: Geng
authors.initials: G
authors.lastname: Li
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D052242:Adiponectin; D003577:Cytochrome P-450 Enzyme System; C106098:Cyp2j3 protein, rat