Wu Chia-Hua, Mohammadmoradi Shayan, Thompson Joel, Su Wen, Gong Ming, Nguyen Genevieve, Yiannikouris Frédérique
From the Department of Pharmacology and Nutritional Sciences (C.-H.W., S.M., F.Y.), Division of Endocrinology and Molecular Medicine (J.T.), and Department of Physiology (W.S., M.G.), University of Kentucky, Lexington; and Institut National de la Santè et de la Recherche Mèdicale (INSERM) U489 and Collège de France, Experimental Medicine Unit, Paris, France (G.N.).
Hypertension. 2016 Jul;68(1):213-9. doi: 10.1161/HYPERTENSIONAHA.115.06954. Epub 2016 May 16.
Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR-deficient mice (PRR(Adi/Y)) with almost no detectable white adipose tissues. As a consequence, the livers of PRR(Adi/Y) mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte-PRR-deficient mice were resistant to diet-induced obesity. Both high-fat- and low-fat-fed PRR(Adi/Y) mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRR(Adi/Y) mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRR(Adi/Y) mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRR(Adi/Y) mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARγ (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation.
与肥胖相关的脂肪组织功能障碍绝大多数与患心血管疾病风险增加有关。在肥胖情况下，小鼠脂肪组织中（前）肾素受体（PRR）增加。我们试图利用脂联素-Cre小鼠确定脂肪细胞PRR缺乏的生理后果。我们报告了一种独特的脂肪细胞PRR缺陷小鼠模型（PRR(Adi/Y)），其几乎检测不到白色脂肪组织。结果，PRR(Adi/Y)小鼠的肝脏肿大，并显示出脂质的明显蓄积。脂肪细胞特异性PRR缺乏会增加收缩压和血浆中可溶性PRR的浓度。为了确定脂肪细胞PRR是否参与肥胖诱导的高血压的发生，给小鼠喂食低脂或高脂饮食16周。脂肪细胞PRR缺陷小鼠对饮食诱导的肥胖具有抗性。高脂和低脂喂养的PRR(Adi/Y)小鼠胰岛素水平均升高。有趣的是，脂肪细胞PRR缺乏改善了高脂喂养的PRR(Adi/Y)小鼠的葡萄糖耐量。无论是喂食低脂还是高脂饮食，PRR(Adi/Y)小鼠的收缩压均高于对照小鼠。高脂喂养会提高对照小鼠和PRR(Adi/Y)小鼠的可溶性PRR浓度。通过小干扰RNA（siRNA）在体外敲低PRR可显著降低过氧化物酶体增殖物激活受体γ（PPARγ）的mRNA丰度，表明PRR在脂肪生成中起重要作用。我们的数据表明，脂肪细胞PRR参与脂质稳态以及葡萄糖和胰岛素稳态，并且可溶性PRR可能是代谢紊乱的预测指标，并在收缩压调节中发挥作用。
