Impact of MR on mature adipocytes in high-fat/high-sucrose diet-induced obesity
Impact of MR on mature adipocytes in high-fat/high-sucrose diet-induced obesity
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DOI：
10.1530/joe-18-0026
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发表时间：
2018-10-01
影响因子：
4
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Hayakawa, Tomoaki;Minemura, Tomomi;Shimomura, Iichiro
肥胖患者脂肪组织中活性糖皮质激素水平升高是由于酶11β-羟基类固醇脱氢酶1。糖皮质激素可以结合和激活糖皮质激素受体(GR)和盐皮质激素受体(MR)，而MR的药物阻断可以预防高脂饮食诱导的肥胖和糖耐量异常。为了确定MR在脂肪细胞中的意义，我们建立了脂肪细胞特异性MR基因敲除小鼠(AdipoMR-KO)，并给它们喂高脂/高糖饮食。我们发现，脂肪细胞特异性MR的缺失不会影响体重、脂肪重量、葡萄糖耐量或胰岛素敏感性。虽然AdipoMR-KO小鼠的肝脏重量略有减轻，但与脂肪生成、脂肪分解、脂肪细胞因子和氧化应激相关的基因的mRNA表达水平在对照组和AdipoMR-KO小鼠之间没有显著差异。结果表明，成熟脂肪细胞中的MR在高脂高糖饮食诱导的肥胖小鼠胰岛素抵抗和炎症反应的调节中起次要作用。
Active glucocorticoid levels are elevated in the adipose tissue of obesity due to the enzyme 11 beta-hydroxysteroid dehydrogenase type 1. Glucocorticoids can bind and activate both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and pharmacological blockades of MR prevent high-fat diet-induced obesity and glucose intolerance. To determine the significance of MR in adipocytes, we generated adipocyte-specific MR-knockout mice (AdipoMR-KO) and fed them high-fat/high-sucrose diet. We found that adipocyte-specific deletion of MR did not affect the body weight, fat weight, glucose tolerance or insulin sensitivity. While liver weight was slightly reduced in AdipoMR-KO, there were no significant differences in the mRNA expression levels of genes associated with lipogenesis, lipolysis, adipocytokines and oxidative stress in adipose tissues between the control and AdipoMR-KO mice. The results indicated that MR in mature adipocytes plays a minor role in the regulation of insulin resistance and inflammation in high-fat/high-sucrose diet-induced obese mice.