title: Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice.
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.
authors.affiliation: 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.).
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Wu
authors.affiliation: 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.).
authors.forename: Shayan
authors.initials: S
authors.lastname: Mohammadmoradi
authors.affiliation: 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.).
authors.forename: Joel
authors.initials: J
authors.lastname: Thompson
authors.affiliation: 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.).
authors.forename: Wen
authors.initials: W
authors.lastname: Su
authors.affiliation: 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.).
authors.forename: Ming
authors.initials: M
authors.lastname: Gong
authors.affiliation: 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.).
authors.forename: Genevieve
authors.initials: G
authors.lastname: Nguyen
authors.affiliation: 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.). fbyian2@uky.edu.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Yiannikouris
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000172:deficiency*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D008060:Lipodystrophy / Q000209:etiology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000503:physiopathology; D011237:Predictive Value of Tests; D011897:Random Allocation
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; D007328:Insulin
keywords: adipocytes; blood pressure; glucose; insulin; lipids; prorenin receptor