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Estrogen‐related receptor β deletion modulates whole‐body energy balance via estrogen‐related receptor γ and attenuates neuropeptide Y gene expression
Author(s) -
Byerly Mardi S.,
Al Salayta Muhannad,
Swanson Roy D.,
Kwon Kiwook,
Peterson Jonathan M.,
Wei Zhikui,
Aja Susan,
Moran Timothy H.,
Blackshaw Seth,
Wong G. William
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12122
Subject(s) - endocrinology , medicine , energy homeostasis , neuropeptide y receptor , receptor , estrogen receptor , biology , estrogen , estrogen related receptor alpha , hindbrain , neuropeptide , central nervous system , cancer , breast cancer
Estrogen‐related receptors ( ERR s) α, β and γ are orphan nuclear hormone receptors with no known ligands. Little is known concerning the role of ERR β in energy homeostasis, as complete ERR β‐null mice die mid‐gestation. We generated two viable conditional ERR β‐null mouse models to address its metabolic function. Whole‐body deletion of ERR β in Sox2‐Cre: ERR β lox/lox mice resulted in major alterations in body composition, metabolic rate, meal patterns and voluntary physical activity levels. Nestin‐Cre: ERR β lox/lox mice exhibited decreased expression of ERR β in hindbrain neurons, the predominant site of expression, decreased neuropeptide Y ( NPY ) gene expression in the hindbrain, increased lean body mass, insulin sensitivity, increased energy expenditure, decreased satiety and decreased time between meals. In the absence of ERR β, increased ERR γ signaling decreased satiety and the duration of time between meals, similar to meal patterns observed for both the Sox2‐Cre: ERR β lox/lox and Nestin‐Cre: ERR β lox/lox strains of mice. Central and/or peripheral ERR γ signaling may modulate these phenotypes by decreasing NPY gene expression. Overall, the relative expression ratio between ERR β and ERR γ may be important in modulating ingestive behavior, specifically satiety, gene expression, as well as whole‐body energy balance.