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 (PRRAdi/Y) with almost no detectable white adipose tissues. As a consequence, the livers of PRRAdi/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 PRRAdi/Y mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRRAdi/Y mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRRAdi/Y mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRRAdi/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.
|Number of pages||7|
|State||Published - Jul 1 2016|
Bibliographical noteFunding Information:
These studies were supported by grants from the American Heart Association (13SDG17230008), the National Institute of General Medical Sciences (P20-GM103527), and the University of Kentucky, Center for Clinical and Translational Sciences (UL1TR000117).
© 2016 American Heart Association, Inc.
- blood pressure
- prorenin receptor
ASJC Scopus subject areas
- Internal Medicine