Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis

Colin N. Young, Donald A. Morgan, Scott D. Butler, Kamal Rahmouni, Susan B. Gurley, Thomas M. Coffman, Allyn L. Mark, Robin L. Davisson

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Objective: Elevations in brain angiotensin-II cause increased energy expenditure and a lean phenotype. Interestingly, the metabolic effects of increased brain angiotensin-II mimic the actions of leptin, suggesting an interaction between the two systems. Here we demonstrate that angiotensin-type 1a receptors (AT1aR) in the subfornical organ (SFO), a forebrain structure emerging as an integrative metabolic center, play a key role in the body weight-reducing effects of leptin via brown adipose tissue (BAT) thermogenesis. Methods: Cre/LoxP technology coupled with targeted viral delivery to the SFO in a mouse line bearing a conditional allele of the Agtr1a gene was utilized to determine the interaction between leptin and SFO AT1aR in metabolic regulation. Results: Selective deletion of AT1aR in the SFO attenuated leptin-induced weight loss independent of changes in food intake or locomotor activity. This was associated with diminished leptin-induced increases in core body temperature, blunted upregulation of BAT thermogenic markers, and abolishment of leptin-mediated sympathetic activation to BAT. Conclusions: These data identify a novel interaction between angiotensin-II and leptin in the control of BAT thermogenesis and body weight, and highlight a previously unrecognized role for the forebrain SFO in metabolic regulation.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
JournalMolecular Metabolism
Volume4
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • Angiotensin
  • Brain
  • Brown adipose tissue
  • Leptin
  • Metabolic regulation
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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