Suppression of Resting Metabolism by the Angiotensin AT2 Receptor

Nicole K Littlejohn; Henry L Keen; Benjamin J Weidemann; Kristin E Claflin; Kevin V Tobin; Kathleen R Markan; Sungmi Park; Meghan C Naber; Francoise A Gourronc; Nicole A Pearson; Xuebo Liu; Donald A Morgan; Aloysius J Klingelhutz; Matthew J Potthoff; Kamal Rahmouni; Curt D Sigmund; Justin L Grobe

doi:10.1016/j.celrep.2016.07.003

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Suppression of Resting Metabolism by the Angiotensin AT2 Receptor

Journal article

Open access

Peer reviewed

Suppression of Resting Metabolism by the Angiotensin AT2 Receptor

Nicole K Littlejohn, Henry L Keen, Benjamin J Weidemann, Kristin E Claflin, Kevin V Tobin, Kathleen R Markan, Sungmi Park, Meghan C Naber, Francoise A Gourronc, Nicole A Pearson, …

Cell reports (Cambridge), Vol.16(6), pp.1548-1560

08/09/2016

DOI: 10.1016/j.celrep.2016.07.003

PMCID: PMC4981564

PMID: 27477281

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Abstract

Activation of the brain renin-angiotensin system (RAS) stimulates energy expenditure through increasing of the resting metabolic rate (RMR), and this effect requires simultaneous suppression of the circulating and/or adipose RAS. To identify the mechanism by which the peripheral RAS opposes RMR control by the brain RAS, we examined mice with transgenic activation of the brain RAS (sRA mice). sRA mice exhibit increased RMR through increased energy flux in the inguinal adipose tissue, and this effect is attenuated by angiotensin II type 2 receptor (AT2) activation. AT2 activation in inguinal adipocytes opposes norepinephrine-induced uncoupling protein-1 (UCP1) production and aspects of cellular respiration, but not lipolysis. AT2 activation also opposes inguinal adipocyte function and differentiation responses to epidermal growth factor (EGF). These results highlight a major, multifaceted role for AT2 within inguinal adipocytes in the control of RMR. The AT2 receptor may therefore contribute to body fat distribution and adipose depot-specific effects upon cardio-metabolic health.

Brain - metabolism

Animals

Receptor, Angiotensin, Type 2 - metabolism

Angiotensin II - metabolism

Adipocytes - metabolism

Mice, Inbred C57BL

Adipose Tissue, White - metabolism

Renin-Angiotensin System - physiology

Energy Metabolism - physiology

Obesity - metabolism

Details

Title: Subtitle: Suppression of Resting Metabolism by the Angiotensin AT2 Receptor
Creators: Nicole K Littlejohn - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Henry L Keen - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Benjamin J Weidemann - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Kristin E Claflin - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Kevin V Tobin - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Kathleen R Markan - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Sungmi Park - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Meghan C Naber - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Francoise A Gourronc - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Nicole A Pearson - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Xuebo Liu - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Donald A Morgan - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Aloysius J Klingelhutz - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA; Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA
Matthew J Potthoff - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA; Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA; Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USA
Kamal Rahmouni - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA; Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA; Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USA; François M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA; Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, USA
Curt D Sigmund - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA; Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA; Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USA; François M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA; Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, USA. Electronic address: curt-sigmund@uiowa.edu
Justin L Grobe - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA; Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA; Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USA; François M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA; Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, USA. Electronic address: justin-grobe@uiowa.edu
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.16(6), pp.1548-1560
DOI: 10.1016/j.celrep.2016.07.003
PMID: 27477281
PMCID: PMC4981564
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: United States
Grant note: R01 DK106104 / NIDDK NIH HHS R00 HL098276 / NHLBI NIH HHS R01 AG027388 / NIA NIH HHS R21 DE019953 / NIDCR NIH HHS K01 DK111758 / NIDDK NIH HHS P01 HL014388 / NHLBI NIH HHS R01 HL048058 / NHLBI NIH HHS P01 HL062984 / NHLBI NIH HHS P01 HL084207 / NHLBI NIH HHS F32 DK102347 / NIDDK NIH HHS R37 HL048058 / NHLBI NIH HHS K99 HL098276 / NHLBI NIH HHS
Language: English
Date published: 08/09/2016
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology; Iowa Neuroscience Institute; Radiation Oncology; Neuroscience and Pharmacology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984001202202771

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