Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany.
Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife 50670-901, Brazil.
Int J Mol Sci. 2024 Sep 1;25(17):9515. doi: 10.3390/ijms25179515.
Angiotensin converting enzyme 2 (ACE2) presents pleiotropic actions. It hydrolyzes angiotensin I (AngI) and angiotensin II (AngII) into angiotensin-(1-9) (Ang-(1-9)) and angiotensin-(1-7) (Ang-(1-7)), respectively, as well as participates in tryptophan uptake in the gut and in COVID-19 infection. Our aim was to investigate the metabolic effect of ACE2 deletion in young adults and elderly mice under conditions of high calorie intake. Male C57Bl/6 (WT) and ACE2-deficient (ACE2) mice were analyzed at the age of 6 and 12 months under standard diet (StD) and high-fat diet (HFD). Under StD, ACE2 showed lower body weight and fat depots, improved glucose tolerance, enhanced insulin sensitivity, higher adiponectin, and lower leptin levels compared to WT. This difference was even more pronounced after HFD in 6-month-old mice, but, interestingly, it was blunted at the age of 12 months. ACE2 presented a decrease in adipocyte diameter and lipolysis, which reflected in the upregulation of lipid metabolism in white adipose tissue through the increased expression of genes involved in lipid regulation. Under HFD, both food intake and total energy expenditure were decreased in 6-month-old ACE2 mice, accompanied by an increase in liquid intake, compared to WT mice, fed either StD or HFD. Thus, ACE2 mice are less susceptible to HFD-induced obesity in an age-dependent manner, as well as represent an excellent animal model of human lipodystrophy and a tool to investigate new treatments.
血管紧张素转换酶 2（ACE2）具有多种作用。它分别将血管紧张素 I（AngI）和血管紧张素 II（AngII）水解为血管紧张素-(1-9)（Ang-(1-9)）和血管紧张素-(1-7)（Ang-(1-7)），同时参与肠道色氨酸摄取和 COVID-19 感染。我们的目的是研究高热量摄入条件下年轻和老年 ACE2 缺失小鼠的代谢效应。雄性 C57Bl/6（WT）和 ACE2 缺失（ACE2）小鼠在标准饮食（StD）和高脂肪饮食（HFD）下分别于 6 个月和 12 个月时进行分析。在 StD 条件下，与 WT 相比，ACE2 表现出较低的体重和脂肪沉积，改善的葡萄糖耐量，增强的胰岛素敏感性，较高的脂联素和较低的瘦素水平。在 6 个月大的 HFD 小鼠中，这种差异更为明显，但有趣的是，在 12 个月大时，这种差异减弱了。ACE2 表现出脂肪细胞直径减小和脂肪分解增加，这反映在白色脂肪组织中脂质代谢的上调，通过参与脂质调节的基因表达增加。在 HFD 下，与 WT 相比，6 个月大的 ACE2 小鼠的食物摄入量和总能量消耗均降低，同时液体摄入量增加，无论喂食 StD 还是 HFD。因此，ACE2 小鼠在年龄依赖性方式下对 HFD 诱导的肥胖的敏感性降低，同时也是人类脂肪营养不良的优秀动物模型，并可用于研究新的治疗方法。
