title: Estrogen receptor-α in medial amygdala neurons regulates body weight.
abstract: Estrogen receptor-α (ERα) activity in the brain prevents obesity in both males and females. However, the ERα-expressing neural populations that regulate body weight remain to be fully elucidated. Here we showed that single-minded-1 (SIM1) neurons in the medial amygdala (MeA) express abundant levels of ERα. Specific deletion of the gene encoding ERα (Esr1) from SIM1 neurons, which are mostly within the MeA, caused hypoactivity and obesity in both male and female mice fed with regular chow, increased susceptibility to diet-induced obesity (DIO) in males but not in females, and blunted the body weight-lowering effects of a glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate. Furthermore, selective adeno-associated virus-mediated deletion of Esr1 in the MeA of adult male mice produced a rapid body weight gain that was associated with remarkable reductions in physical activity but did not alter food intake. Conversely, overexpression of ERα in the MeA markedly reduced the severity of DIO in male mice. Finally, an ERα agonist depolarized MeA SIM1 neurons and increased their firing rate, and designer receptors exclusively activated by designer drug-mediated (DREADD-mediated) activation of these neurons increased physical activity in mice. Collectively, our results support a model where ERα signals activate MeA neurons to stimulate physical activity, which in turn prevents body weight gain.
authors.forename: Pingwen
authors.initials: P
authors.lastname: Xu
authors.forename: Xuehong
authors.initials: X
authors.lastname: Cao
authors.forename: Yanlin
authors.initials: Y
authors.lastname: He
authors.forename: Liangru
authors.initials: L
authors.lastname: Zhu
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Yang
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yan
authors.forename: Antentor Othrell
authors.initials: AO
authors.lastname: Hinton
authors.forename: Fang
authors.initials: F
authors.lastname: Zou
authors.forename: Hongfang
authors.initials: H
authors.lastname: Ding
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Chunling
authors.initials: C
authors.lastname: Yan
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
authors.forename: San-Pin
authors.initials: SP
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Feng
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Clegg
authors.forename: Richard
authors.initials: R
authors.lastname: DeMarchi
authors.forename: Sohaib A
authors.initials: SA
authors.lastname: Khan
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000502:physiology*; D066276:Corticomedial Nuclear Complex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction; D015430:Weight Gain / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D052216:Glucagon-Like Peptide 1; D012097:Repressor Proteins; C101750:Sim1 protein, mouse