Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain.
CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain.
Cells. 2019 Nov 19;8(11):1464. doi: 10.3390/cells8111464.
A differential sex-related sensitivity has been reported in obesity and insulin resistance-related cardio-metabolic diseases, with a lower incidence of these pathologies being observed in young females when compared to age-matched males. However, such relative protection is lost with age. The mechanisms underlying such sex and age-related changes in the susceptibility to diabetes and obesity are not fully understood. Herein, we report that the relative protection that is displayed by young female mice, as compared to male littermates, against some of the metabolic alterations that are induced by feeding a high fat diet (HFD), correlates with a lower upregulation of the protein levels of G protein-coupled receptor kinase (GRK2), which is a key regulator of both insulin and G protein-coupled receptor signaling, in the liver and adipose tissue. Interestingly, when the HFD is initiated in middle-aged (32 weeks) female mice, these animals are no longer protected and display a more overt obese and insulin-resistant phenotype, along with a more evident increase in the GRK2 protein levels in metabolically relevant tissues in such conditions. Our data suggest that GRK2 dosage might be involved in the sex and age-biased sensitivity to insulin resistance-related pathologies.
在肥胖和与胰岛素抵抗相关的心代谢疾病中，已经报道了性别相关的敏感性差异，与年龄匹配的男性相比，年轻女性这些病理的发病率较低。然而，这种相对保护随着年龄的增长而丧失。性别和年龄相关的糖尿病和肥胖易感性变化的机制尚未完全阐明。在此，我们报告称，与雄性同窝仔相比，年轻雌性小鼠对高脂肪饮食（HFD）诱导的一些代谢改变的相对保护作用与肝脏和脂肪组织中 G 蛋白偶联受体激酶（GRK2）的蛋白水平下调相关，GRK2 是胰岛素和 G 蛋白偶联受体信号的关键调节剂。有趣的是，当中年（32 周）雌性小鼠开始食用 HFD 时，这些动物不再受到保护，表现出更为明显的肥胖和胰岛素抵抗表型，同时在这种情况下，代谢相关组织中 GRK2 蛋白水平的增加更为明显。我们的数据表明，GRK2 剂量可能参与了性别和年龄对与胰岛素抵抗相关病理的敏感性差异。
