Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Diabetes Care Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
J Endocrinol. 2018 Oct 1;239(1):63–71. doi: 10.1530/JOE-18-0026.
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.
由于酶 11β-羟甾类脱氢酶 1 的存在，肥胖患者的脂肪组织中活性糖皮质激素水平升高。糖皮质激素可以与糖皮质激素受体 (GR) 和盐皮质激素受体 (MR) 结合并激活它们，而 MR 的药理学阻断可以预防高脂肪饮食诱导的肥胖和葡萄糖不耐受。为了确定 MR 在脂肪细胞中的意义，我们生成了脂肪细胞特异性 MR 敲除小鼠 (AdipoMR-KO) 并喂食它们高脂肪/高蔗糖饮食。我们发现，脂肪细胞特异性 MR 缺失并不影响体重、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，但对照组和 AdipoMR-KO 小鼠的脂肪组织中与脂肪生成、脂肪分解、脂肪细胞因子和氧化应激相关的基因的 mRNA 表达水平没有显著差异。结果表明，成熟脂肪细胞中的 MR 在高脂肪/高蔗糖饮食诱导的肥胖小鼠中对胰岛素抵抗和炎症的调节作用较小。
