Journal article
Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism
The Journal of clinical investigation, Vol.127(4), pp.1414-1424
04/03/2017
DOI: 10.1172/JCI88641
PMCID: PMC5373887
PMID: 28263184
Abstract
Leptin contributes to the control of resting metabolic rate (RMR) and blood pressure (BP) through its actions in the arcuate nucleus (ARC). The renin-angiotensin system (RAS) and angiotensin AT
1
receptors within the brain are also involved in the control of RMR and BP, but whether this regulation overlaps with leptin’s actions is unclear. Here, we have demonstrated the selective requirement of the AT
1A
receptor in leptin-mediated control of RMR. We observed that AT
1A
receptors colocalized with leptin receptors (LEPRs) in the ARC. Cellular coexpression of AT
1A
and LEPR was almost exclusive to the ARC and occurred primarily within neurons expressing agouti-related peptide (AgRP). Mice lacking the AT
1A
receptor specifically in LEPR-expressing cells failed to show an increase in RMR in response to a high-fat diet and deoxycorticosterone acetate–salt (DOCA-salt) treatments, but BP control remained intact. Accordingly, loss of RMR control was recapitulated in mice lacking AT
1A
in AgRP-expressing cells. We conclude that angiotensin activates divergent mechanisms to control BP and RMR and that the brain RAS functions as a major integrator for RMR control through its actions at leptin-sensitive AgRP cells of the ARC.
Details
- Title: Subtitle
- Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism
- Creators
- Kristin E Claflin - Department of PharmacologyJeremy A Sandgren - Department of PharmacologyAllyn M Lambertz - Department of PathologyBenjamin J Weidemann - Department of PharmacologyNicole K Littlejohn - Department of PharmacologyColin M.L Burnett - Department of PharmacologyNicole A Pearson - Department of PharmacologyDonald A Morgan - Department of PharmacologyKatherine N Gibson-Corley - Department of PathologyKamal Rahmouni - Department of PharmacologyJustin L Grobe - Department of Pharmacology
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.127(4), pp.1414-1424
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI88641
- PMID
- 28263184
- PMCID
- PMC5373887
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 04/03/2017
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984040282902771
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