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

doi:10.1016/j.molmet.2015.01.007

Back

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

Journal article

Open access

Peer reviewed

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 and Robin L Davisson

Molecular metabolism (Germany), Vol.4(4), pp.337-343

04/2015

DOI: 10.1016/j.molmet.2015.01.007

PMCID: PMC4354922

PMID: 25830096

Files and links (1)

url

https://doi.org/10.1016/j.molmet.2015.01.007View

Published (Version of record) Open Access

Abstract

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. 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. 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. 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.

Metabolic regulation

Brain

Brown adipose tissue

Sympathetic nervous system

Leptin

Angiotensin

Details

Title: Subtitle: Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis
Creators: Colin N Young - Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
Donald A Morgan - Department of Pharmacology, University of Iowa, Iowa City, IA, 52242, USA
Scott D Butler - Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
Kamal Rahmouni - Department of Pharmacology, University of Iowa, Iowa City, IA, 52242, USA
Susan B Gurley - Division of Nephrology, Department of Medicine, Duke University, Durham, NC 27710, USA
Thomas M Coffman - Division of Nephrology, Department of Medicine, Duke University, Durham, NC 27710, USA
Allyn L Mark - Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA
Robin L Davisson - Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
Resource Type: Journal article
Publication Details: Molecular metabolism (Germany), Vol.4(4), pp.337-343
DOI: 10.1016/j.molmet.2015.01.007
PMID: 25830096
PMCID: PMC4354922
NLM abbreviation: Mol Metab
ISSN: 2212-8778
eISSN: 2212-8778
Publisher: Elsevier GmbH
Grant note: name: NIH, award: HL84207, HL63887, K99HL166776; DOI: 10.13039/100005384, name: American Physiological Society; DOI: 10.13039/100000968, name: American Heart Association, award: 13POST14410020
Language: English
Date published: 04/2015
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040232202771

Metrics

21 Record Views

23 Times Cited - Web of Science