Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice. Issue 1 (July 2016)

• Record Type: Journal Article
• Authors: Wu, Chia-Hua; Mohammadmoradi, Shayan; Thompson, Joel; Su, Wen; Gong, Ming; Nguyen, Genevieve; Yiannikouris, Frédérique
• Is Part Of: Hypertension. Volume 68:Issue 1(2016:Jul.)
• Publication Date: 2016-07
• Subjects: adipocytes -- blood pressure -- glucose -- insulin -- lipids -- prorenin receptor; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.115.06954
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.