Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis

Kathryn E. Davis, Elizabeth J. Carstens, Boman G. Irani, Lana M. Gent, Lisa M. Hahner, Deborah J. Clegg

Research output: Contribution to journalReview article

42 Citations (Scopus)

Abstract

This article is part of a Special Issue "Energy Balance".The classical estrogen receptors, estrogen receptor-α and estrogen receptor-β are well established in the regulation of body weight and energy homeostasis in both male and female mice, whereas, the role for G protein-coupled estrogen receptor 1 (GPER) as a modulator of energy homeostasis remains controversial. This study sought to determine whether gene deletion of GPER (GPER KO) alters body weight, body adiposity, food intake, and energy homeostasis in both males and females. Male mice lacking GPER developed moderate obesity and larger adipocyte size beginning at 8. weeks of age, with significant reductions in energy expenditure, but not food intake or adipocyte number. Female GPER KO mice developed increased body weight relative to WT females a full 6. weeks later than the male GPER KO mice. Female GPER KO mice also had reductions in energy expenditure, but no significant increases in body fat content. Consistent with their decrease in energy expenditure, GPER KO males and females showed significant reductions in two brown fat thermogenic proteins. GPER KO females, prior to their divergence in body weight, were less sensitive than WT females to the feeding-inhibitory effects of leptin and CCK. Additionally, body weight was not as modulated by ovariectomy or estradiol replacement in GPER KO mice. Estradiol treatment activated phosphorylated extracellular signal-regulated kinase (pERK) in WT but not GPER KO females. For the first time, GPER expression was found in the adipocyte but not the stromal fraction of adipose tissue. Together, these results provide new information elucidating a sexual dimorphism in GPER function in the development of postpubertal energy balance.

Original languageEnglish (US)
Pages (from-to)196-207
Number of pages12
JournalHormones and Behavior
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

G-Protein-Coupled Receptors
Estrogen Receptors
Homeostasis
Body Weight
Adipocytes
Energy Metabolism
Adipose Tissue
Estradiol
Eating
Brown Adipose Tissue
Estrogen Receptor alpha
Extracellular Signal-Regulated MAP Kinases
Gene Deletion
Adiposity
Ovariectomy
Leptin
Sex Characteristics
Obesity

Keywords

  • Adiposity
  • Cholecystokinin
  • Estrogen receptor-α
  • G protein coupled receptor 30
  • Leptin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. / Davis, Kathryn E.; Carstens, Elizabeth J.; Irani, Boman G.; Gent, Lana M.; Hahner, Lisa M.; Clegg, Deborah J.

In: Hormones and Behavior, Vol. 66, No. 1, 01.01.2014, p. 196-207.

Research output: Contribution to journalReview article

Davis, Kathryn E. ; Carstens, Elizabeth J. ; Irani, Boman G. ; Gent, Lana M. ; Hahner, Lisa M. ; Clegg, Deborah J. / Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. In: Hormones and Behavior. 2014 ; Vol. 66, No. 1. pp. 196-207.
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