Journal article
Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism
Hypertension (Dallas, Tex. 1979), Vol.70(5), pp.990-997
11/2017
DOI: 10.1161/HYPERTENSIONAHA.117.09923
PMCID: PMC5679092
PMID: 28874461
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
mice exhibited central RAS activation and hypertension through increased expression of Ren-a, but the dipsogenic and metabolic effects in Ren-b
mice are unknown. Fluid intake was similar in control and Ren-b
mice at baseline and both exhibited an equivalent dipsogenic response to deoxycorticosterone acetate-salt. Dehydration promoted increased water intake in Ren-b
mice, particularly after deoxycorticosterone acetate-salt. Ren-b
and control mice exhibited similar body weight when fed a chow diet. However, when fed a high-fat diet, male Ren-b
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
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
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.
Details
- Title: Subtitle
- Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism
- Creators
- Keisuke Shinohara - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Pablo Nakagawa - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Javier Gomez - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Donald A Morgan - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Nicole K Littlejohn - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Matthew D Folchert - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Benjamin J Weidemann - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Xuebo Liu - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Susan A Walsh - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Laura L Ponto - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Kamal Rahmouni - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Justin L Grobe - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.)Curt D Sigmund - From the Departments of Pharmacology (K.S., P.N., J.G., D.A.M., N.K.L., M.D.F., B.J.W., X.L., K.R., J.L.G., C.D.S.), Radiology (S.A.W., L.L.P.), and UIHC Center for Hypertension Research, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City (K.R., J.L.G., C.D.S.). curt-sigmund@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.70(5), pp.990-997
- Publisher
- United States
- DOI
- 10.1161/HYPERTENSIONAHA.117.09923
- PMID
- 28874461
- PMCID
- PMC5679092
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- R01 HL125603 / NHLBI NIH HHS R00 HL098276 / NHLBI NIH HHS T35 HL007485 / NHLBI NIH HHS R01 HL131689 / NHLBI NIH HHS S10 RR025036 / NCRR NIH HHS P01 HL084207 / NHLBI NIH HHS R01 HL134850 / NHLBI NIH HHS P30 CA086862 / NCI NIH HHS K99 HL098276 / NHLBI NIH HHS
- Language
- English
- Date published
- 11/2017
- Academic Unit
- Radiology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040277902771
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