Faculty Collaboration Database

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism. Hypertension 2017 Nov;70(5):990-997

Date

09/07/2017

Pubmed ID

28874461

Pubmed Central ID

PMC5679092

DOI

10.1161/HYPERTENSIONAHA.117.09923

Scopus ID

2-s2.0-85031820971 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

The brain-specific isoform of renin (Ren-b) has been proposed as a negative regulator of the brain renin-angiotensin system (RAS). We analyzed mice with a selective deletion of Ren-b which preserved expression of the classical renin (Ren-a) isoform. We reported that Ren-b^Null mice exhibited central RAS activation and hypertension through increased expression of Ren-a, but the dipsogenic and metabolic effects in Ren-b^Null mice are unknown. Fluid intake was similar in control and Ren-b^Null mice at baseline and both exhibited an equivalent dipsogenic response to deoxycorticosterone acetate-salt. Dehydration promoted increased water intake in Ren-b^Null mice, particularly after deoxycorticosterone acetate-salt. Ren-b^Null and control mice exhibited similar body weight when fed a chow diet. However, when fed a high-fat diet, male Ren-b^Null mice gained significantly less weight than control mice, an effect blunted in females. This difference was not because of changes in food intake, energy absorption, or physical activity. Ren-b^Null mice exhibited increased resting metabolic rate concomitant with increased uncoupled protein 1 expression and sympathetic nerve activity to the interscapular brown adipose tissue, suggesting increased thermogenesis. Ren-b^Null mice were modestly intolerant to glucose and had normal insulin sensitivity. Another mouse model with markedly enhanced brain RAS activity (sRA mice) exhibited pronounced insulin sensitivity concomitant with increased brown adipose tissue glucose uptake. Altogether, these data support the hypothesis that the brain RAS regulates energy homeostasis by controlling resting metabolic rate, and that Ren-b deficiency increases brain RAS activity. Thus, the relative level of expression of Ren-b and Ren-a may control activity of the brain RAS.

Author List

Shinohara K, Nakagawa P, Gomez J, Morgan DA, Littlejohn NK, Folchert MD, Weidemann BJ, Liu X, Walsh SA, Ponto LL, Rahmouni K, Grobe JL, Sigmund CD

Authors

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Basal Metabolism
Brain
Drinking
Energy Metabolism
Hypertension
Mice
Protein Isoforms
Renin
Renin-Angiotensin System
Sympathetic Nervous System