Renal (Pro)renin Receptor Contributes to High Fat Diet-Induced Obesity

Abstract

Abstract Recently we reported that (Pro)renin receptor (PRR) expression increases in the renal nephron during high fat diet intake. This study evaluated the role of renal PRR in the development of obesity. Eight-week old male mice with inducible nephron specific PRR knockout (KO) and wild type littermate (control) were fed either normal diet (ND, 12%kcal fat) or high fat diet (HFD, 45%kcal fat) for 6 months. KO Mice underwent induction of PRR KO with oral doxycycline 2mg/mL in 2% sucrose water for 12 days prior to starting diet. Compared to ND, HFD increased body weight by 40% (p<0.05) in control mice. In contrast, compared to control mice fed HFD, body weight of induced PRR KO on HFD was reduced by 56% (p<0.05). Total body fat increased by 179% (p<0.05) with HFD compared to ND control mice while it did not increase in PRR KO mice fed HFD. Twenty-four-hour caloric intake was not reduced in KO mice compared to controls while there were significant increases in nocturnal VO2 by 31% and respiratory exchange by 10% (p<0.05) in HFD PRR KO mice compared to HFD fed controls. Unexpectedly, urine glucose excretion significantly increased in PRR KO mice on both ND and HFD. Our results demonstrate that nephron specific PRR KO reduced diet induced obesity and adiposity, while increasing energy expenditure. Future investigations are warranted to elucidate the mechanisms by which renal PRR contributes to the development of obesity.