Format

Send to

Choose Destination
Hypertension. 2016 Jul;68(1):213-9. doi: 10.1161/HYPERTENSIONAHA.115.06954. Epub 2016 May 16.

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

Author information

1
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.).
2
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.

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.

KEYWORDS:

adipocytes; blood pressure; glucose; insulin; lipids; prorenin receptor

PMID:
27185751
PMCID:
PMC4900901
DOI:
10.1161/HYPERTENSIONAHA.115.06954
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center