Saito, KenjiHe, YanlinYang, YongjieZhu, LiangruWang, ChunmeiXu, PingwenHinton, Antentor OthrellYan, XiaofengZhao, JeanFukuda, MakotoTong, QingchunClegg, Deborah J.Xu, Yong2016-04-012016Saito, K., Y. He, Y. Yang, L. Zhu, C. Wang, P. Xu, A. O. Hinton, et al. 2016. “PI3K in the ventromedial hypothalamic nucleus mediates estrogenic actions on energy expenditure in female mice.” Scientific Reports 6 (1): 23459. doi:10.1038/srep23459. http://dx.doi.org/10.1038/srep23459.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318571Estrogens act in the ventromedial hypothalamic nucleus (VMH) to regulate body weight homeostasis. However, the molecular mechanisms underlying these estrogenic effects are unknown. We show that activation of estrogen receptor-α (ERα) stimulates neural firing of VMH neurons expressing ERα, and these effects are blocked with intracellular application of a pharmacological inhibitor of the phosphatidyl inositol 3-kinase (PI3K). Further, we demonstrated that mice with genetic inhibition of PI3K activity in VMH neurons showed a sexual dimorphic obese phenotype, with only female mutants being affected. In addition, inhibition of VMH PI3K activity blocked effects of 17β-estradiol to stimulate energy expenditure, but did not affect estrogen-induced anorexia. Collectively, our results indicate that PI3K activity in VMH neurons plays a physiologically relevant role in mediating estrogenic actions on energy expenditure in females.en-USJournal Article2016-04-0110.1038/srep23459