Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism
| Autor: | Curt D. Sigmund, Matthew D Folchert, Kamal Rahmouni, Nicole K. Littlejohn, Javier Gomez, Justin L. Grobe, Pablo Nakagawa, Benjamin J. Weidemann, Laura L. Boles Ponto, Susan A. Walsh, Donald A. Morgan, Xuebo Liu, Keisuke Shinohara |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Sympathetic Nervous System Glucose uptake medicine.medical_treatment Drinking Adipose tissue 030204 cardiovascular system & hematology Biology Energy homeostasis Article Renin-Angiotensin System 03 medical and health sciences Mice 0302 clinical medicine Internal medicine Brown adipose tissue Renin Internal Medicine medicine Animals Protein Isoforms Insulin Brain Angiotensin II 030104 developmental biology Endocrinology medicine.anatomical_structure Basal metabolic rate Hypertension Basal Metabolism Energy Metabolism Thermogenesis |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 70(5) |
| ISSN: | 1524-4563 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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