TY - JOUR
T1 - Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis
AU - Davis, Kathryn E.
AU - Carstens, Elizabeth J.
AU - Irani, Boman G.
AU - Gent, Lana M.
AU - Hahner, Lisa M.
AU - Clegg, Deborah J.
N1 - Funding Information:
We thank Dr. Roger Unger for providing us the human leptin. We also thank Dr. Nedungadi for performing the leptin and insulin assays. This work was supported by the National Institute of Health grant numbers DK073689 and DK088761 .
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Adiposity
KW - Cholecystokinin
KW - Estrogen receptor-α
KW - G protein coupled receptor 30
KW - Leptin
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U2 - 10.1016/j.yhbeh.2014.02.004
DO - 10.1016/j.yhbeh.2014.02.004
M3 - Review article
C2 - 24560890
AN - SCOPUS:84901836534
SN - 0018-506X
VL - 66
SP - 196
EP - 207
JO - Hormones and Behavior
JF - Hormones and Behavior
IS - 1
ER -