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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #319736

Research Project: Developmental Determinants of Obesity in Infants and Children

Location: Children's Nutrition Research Center

Title: Estrogen receptor-a in medial amygdala neurons regulates body weight

Author
item Xu, Pingwen - Children'S Nutrition Research Center (CNRC)
item Cao, Xuehong - Children'S Nutrition Research Center (CNRC)
item He, Yanlin - Children'S Nutrition Research Center (CNRC)
item Zhu, Liangru - Children'S Nutrition Research Center (CNRC)
item Yang, Yongjie - Children'S Nutrition Research Center (CNRC)
item Saito, Kenji - Children'S Nutrition Research Center (CNRC)
item Wang, Chunmei - Children'S Nutrition Research Center (CNRC)
item Yan, Xiaofeng - Children'S Nutrition Research Center (CNRC)
item Hinton, Antentor - Children'S Nutrition Research Center (CNRC)
item Zou, Fang - Children'S Nutrition Research Center (CNRC)
item Ding, Hongfang - Children'S Nutrition Research Center (CNRC)
item Xia, Yan - Children'S Nutrition Research Center (CNRC)
item Yan, Chunling - Children'S Nutrition Research Center (CNRC)
item Shu, Gang - Children'S Nutrition Research Center (CNRC)
item Wu, San-pin - Baylor College Of Medicine
item Yang, Bin - Indiana University
item Feng, Yuxin - University Of Cincinnati
item Clegg, Deborah - Cedars-Sinai Medical Center
item Dimarchi, Richard - Indiana University
item Khan, Sohaib - University Of Cincinnati
item Tsai, Sophia - Baylor College Of Medicine
item Demayo, Francesco - Baylor College Of Medicine
item Wu, Qi - Children'S Nutrition Research Center (CNRC)
item Tong, Qingchun - University Of Houston
item Xu, Yong - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/8/2015
Publication Date: 7/22/2015
Citation: Xu, P., Cao, X., He, Y., Zhu, L., Yang, Y., Saito, K., Wang, C., Yan, X., Hinton, A., Zou, F., Ding, H., Xia, Y., Yan, C., Shu, G., Wu, S., Yang, B., Feng, Y., Clegg, D.J., Dimarchi, R., Khan, S., Tsai, S., Demayo, F., Wu, Q., Tong, Q., Xu, Y. 2015. Estrogen receptor-a in medial amygdala neurons regulates body weight. Journal of Clinical Investigation. 125(7):2861-2876.

Interpretive Summary: Obesity is a serious global health problem. Here we showed that the female sex hormone, estrogen, can reduce body weight in both female and male mice through its actions in a brain region, called medial amygdala. These findings suggested that estrogen signals in this brain region could be a potential target for treatment of obesity.

Technical Abstract: Estrogen receptor–a (ERa) activity in the brain prevents obesity in both males and females. However, the ERa-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 ERa. Specific deletion of the gene encoding ERa (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 ERa in the MeA markedly reduced the severity of DIO in male mice. Finally, an ERa 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 ERa signals activate MeA neurons to stimulate physical activity, which in turn prevents body weight gain.