Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice.
Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice.
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DOI：
10.1016/j.cmet.2011.05.009
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发表时间：
2011-07
期刊：
影响因子：
29
通讯作者：
W. Wong;X. Tian;A. Xu;Jun Yu;C. Lau;R. L. Hoo;Yu Wang;V. W. Lee;K. Lam;P. Vanhoutte;
中科院分区：
文献类型：
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作者：
W. Wong;X. Tian;A. Xu;Jun Yu;C. Lau;R. L. Hoo;Yu Wang;V. W. Lee;K. Lam;P. Vanhoutte;
罗格列酮是一种常用于治疗糖尿病的PPARγ激动剂。除了改善胰岛素敏感性外，罗格列酮还通过一种机制恢复正常血管功能，这种机制目前尚不清楚。在这里，我们表明脂联素是介导PPARγ对糖尿病小鼠血管内皮作用所必需的。在db/db和饮食诱导的肥胖小鼠中，罗格列酮激活的PPARγ可恢复血管内皮依赖性舒张，而缺乏脂联素或用抗脂联素抗体治疗的糖尿病小鼠则无反应。罗格列酮刺激脂肪外植体释放脂联素，罗格列酮治疗小鼠皮下脂肪移植重现未治疗db/db受体的血管舒张。脂联素在体内激活AMPK/eNOS和cAMP/PKA信号通路，增加NO生物利用度，降低氧化应激。综上所述，这些结果表明，脂肪细胞衍生的脂联素是糖尿病中PPARγ介导的内皮功能改善所必需的。因此，脂肪组织代表了治疗糖尿病血管病变的有希望的靶点。
Rosiglitazone is a PPARγ agonist commonly used to treat diabetes. In addition to improving insulin sensitivity, rosiglitazone restores normal vascular function by a mechanism that remains poorly understood. Here we show that adiponectin is required to mediate the PPARγ effect on vascular endothelium of diabetic mice. In db/db and diet-induced obese mice, PPARγ activation by rosiglitazone restores endothelium-dependent relaxation of aortae, whereas diabetic mice lacking adiponectin or treated with an anti-adiponectin antibody do not respond. Rosiglitazone stimulates adiponectin release from fat explants, and subcutaneous fat transplantation from rosiglitazone-treated mice recapitulates vasodilatation in untreated db/db recipients. Mechanistically, adiponectin activates AMPK/eNOS and cAMP/PKA signaling pathways in aortae, which increase NO bioavailability and reduce oxidative stress. Taken together, these results demonstrate that adipocyte-derived adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetes. Thus, the adipose tissue represents a promising target for treating diabetic vasculopathy.