The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance. Cell Metab 2010 Nov 03;12(5):431-42
Date
11/03/2010Pubmed ID
21035755Pubmed Central ID
PMC2994017DOI
10.1016/j.cmet.2010.09.011Scopus ID
2-s2.0-78049448391 (requires institutional sign-in at Scopus site) 125 CitationsAbstract
The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.
Author List
Grobe JL, Grobe CL, Beltz TG, Westphal SG, Morgan DA, Xu D, de Lange WJ, Li H, Sakai K, Thedens DR, Cassis LA, Rahmouni K, Mark AL, Johnson AK, Sigmund CDAuthors
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinCurt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adrenal GlandsAngiotensin II
Angiotensinogen
Animals
Brain
Energy Metabolism
Gene Expression
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Polyuria
Promoter Regions, Genetic
Renin
Renin-Angiotensin System
Steroids
Sympathetic Nervous System
Synapsins
Thermogenesis