The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance

Justin L. Grobe, Connie L. Grobe, Terry G. Beltz, Scott G. Westphal, Donald A. Morgan, Di Xu, Willem J. De Lange, Huiping Li, Koji Sakai, Daniel R. Thedens, Lisa A. Cassis, Kamal Rahmouni, Allyn L. Mark, Alan Kim Johnson, Curt D. Sigmund

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)431-442
Number of pages12
JournalCell Metabolism
Volume12
Issue number5
DOIs
StatePublished - Nov 3 2010

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Grobe, J. L., Grobe, C. L., Beltz, T. G., Westphal, S. G., Morgan, D. A., Xu, D., De Lange, W. J., Li, H., Sakai, K., Thedens, D. R., Cassis, L. A., Rahmouni, K., Mark, A. L., Johnson, A. K., & Sigmund, C. D. (2010). The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance. Cell Metabolism, 12(5), 431-442. https://doi.org/10.1016/j.cmet.2010.09.011