title: Suppression of Resting Metabolism by the Angiotensin AT2 Receptor.
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.
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Littlejohn
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Henry L
authors.initials: HL
authors.lastname: Keen
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Weidemann
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Claflin
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Tobin
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Markan
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Sungmi
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Naber
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Francoise A
authors.initials: FA
authors.lastname: Gourronc
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Pearson
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morgan
authors.affiliation: 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.
authors.forename: Aloysius J
authors.initials: AJ
authors.lastname: Klingelhutz
authors.affiliation: 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.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Potthoff
authors.affiliation: 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.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.affiliation: 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.
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
authors.affiliation: 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.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grobe
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II