CYP2J3 gene delivery up-regulated adiponectin expression via reduced endoplasmic reticulum stress in adipocytes.
CYP2J3 gene delivery up-regulated adiponectin expression via reduced endoplasmic reticulum stress in adipocytes.
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DOI：
10.1210/en.2012-2012
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发表时间：
2013-03
期刊：
影响因子：
4.8
通讯作者：
Xizhen Xu;L. Tu;W. Feng;Ben Ma;Rui Li;Changlong Zheng;Geng Li;Daowen Wang
中科院分区：
文献类型：
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作者：
Xizhen Xu;L. Tu;W. Feng;Ben Ma;Rui Li;Changlong Zheng;Geng Li;Daowen Wang
大量证据表明，细胞色素P450(CYP)环氧合酶将花生四烯酸代谢成环氧二十碳三烯酸(EETs)，后者在心血管内稳态中发挥着重要而多样的作用。我们和其他人已经确认EETs在胰岛素抵抗和糖尿病方面发挥了有益的作用。本研究探讨了CYP2J3环氧合酶基因导入对高脂饮食大鼠脂联素表达的影响。体内注射CYP2J3基因可增加EET的生成，增加脂联素的表达和分泌，并伴随脂联素下游信号通路的激活，降低胰岛素抵抗(以血浆胰岛素水平、胰岛素抵抗指数和糖耐量试验为指标)，以及肝脏和肌肉中蛋白激酶B的磷酸化。此外，CYP2J3过表达可预防HF饮食诱导的大鼠脂肪组织内质网(ER)应激。另外，在分化的3T3-L1脂肪细胞中，CYP2J3基因转染和外源性EETs的应用抑制了thapsigargin诱导的内质网应激，并增加了脂联素的表达和分泌。因此，携带CYP2J3基因可通过抑制内质网应激，上调HF饮食大鼠脂肪组织脂联素的表达和分泌，从而降低脂联素的表达。这些结果进一步强调了CYP环氧合酶2J3及其代谢产物EETs对脂联素表达和分泌的有益作用。
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.