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Mol Metab. 2015 Jan 31;4(4):337-43. doi: 10.1016/j.molmet.2015.01.007. eCollection 2015 Apr.

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

Author information

1
Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
2
Department of Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.
3
Division of Nephrology, Department of Medicine, Duke University, Durham, NC 27710, USA.
4
Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA ; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, 10065, USA.
5
Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA ; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, 10065, USA.

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.

KEYWORDS:

AT1aR, angiotensin type 1a receptor; Ang-II, angiotensin-II; Angiotensin; BAT, brown adipose tissue; Brain; Brown adipose tissue; CNS, central nervous system; LepRb, leptin receptor; Leptin; Metabolic regulation; OVLT, organum vasculosum lamina terminalis; RAS, renin-angiotensin system; SFO, subfornical organ; SNA, sympathetic nerve activity; Sympathetic nervous system

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