The role of hypothalamic estrogen receptors in metabolic regulation |
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Authors: | Aaron Frank Lynda M. Brown Deborah J. Clegg |
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Affiliation: | 1. Food and Nutrition Sciences Program, North Carolina Agricultural and Technical State University, Greensboro, NC 27411-0002, USA;2. Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8854, USA |
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Abstract: | Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. |
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Keywords: | AgRP, agouti-related peptide Akt/PKB, protein kinase B ARC, arcuate nucleus CCK, cholecystokinin CNS, central nervous system E2, 17β-estradiol ER, estrogen receptor ERE, estrogen response element ERS1, ER alpha ERS1&minus /&minus , ER alpha null mouse ERKO, ER knock-out mouse ERαKO, ER alpha knockout mouse ERS2, ER beta HPG, hypothalamic pituitary gonadal axis Ghsr&minus /&minus , GHSR null mice GHSRs, growth hormone secretagogue receptors GPCR, G protein-coupled receptor GPER, G protein-coupled ER i3vt, intra-third ventricular leprb, long form of the leptin receptor LHA, lateral hypothalamic area αMSH, alpha melanocyte stimulating hormone MAP, mitogen-activated protein MC3/MC4, melanocortin-3, -4 receptors MCH, melanin-concentrating hormone MNAR, modulator of nongenomic activity of ER MPOA, medial preoptic area NERKI, nuclear ERα knock-in mouse NPY, neuropeptide Y NTS, nucleus of the solitary tract OVX, ovariectomy PI3K, phosphatidylinositol 3-kinase POMC, pro-opiomelanocortin PVN, paraventricular nucleus SF1, steroidogenic factor-1 sh, short hairpin VMH, ventromedial hypothalamus ZI, zona incerta |
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