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Research Project: Developmental Determinants of Obesity in Infants and Children

Location: Children's Nutrition Research Center

Title: Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction

Author
item Xu, Pingwen - Children's Nutrition Research Center (CNRC)
item Zhu, Liangru - Children's Nutrition Research Center (CNRC)
item Saito, Kenji - Children's Nutrition Research Center (CNRC)
item Yang, Yongjie - Children's Nutrition Research Center (CNRC)
item Wang, Chunmei - Children's Nutrition Research Center (CNRC)
item He, Yanlin - Children's Nutrition Research Center (CNRC)
item Yan, Xiaofeng - Children's Nutrition Research Center (CNRC)
item Hyseni, Ilirjana - Children's Nutrition Research Center (CNRC)
item Tong, Qingchun - University Of Texas Health Science Center
item Xu, Yong - Children's Nutrition Research Center (CNRC)

Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2016
Publication Date: 5/1/2017
Citation: Xu, P., Zhu, L., Saito, K., Yang, Y., Wang, C., He, Y., Yan, X., Hyseni, I., Tong, Q., Xu, Y. 2017. Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction. Metabolism. 70:152-159.

Interpretive Summary: Obesity is a serious global health problem. Estrogens, the female sex hormone, have been shown to prevent obesity in female animals. Here we showed that effects of estrogens persist in obese animals that carry MC4R mutations. These findings suggest that estrogens could be a potential target for treatment of obesity in obese patients with MC4R mutations.

Technical Abstract: Brain estrogen receptor-a (ERa) is essential for estrogenic regulation of energy homeostasis and reproduction. We previously showed that ERa expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's effects on food intake, body weight, negative regulation of hypothalamic–pituitary–gonadal axis (HPG axis) and fertility. We report here that global deletion of a key downstream receptor for POMC peptide, the melanocortin 4 receptor (MC4R), did not affect normal negative feedback regulation of estrogen on the HPG axis, estrous cyclicity and female fertility. Furthermore, loss of the MC4R did not influence estrogenic regulation on food intake and body weight. These results indicate that the MC4R is not required for estrogen's effects on metabolic and reproductive functions.