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Sci Rep. 2016 Mar 18;6:23459. doi: 10.1038/srep23459.

PI3K in the ventromedial hypothalamic nucleus mediates estrogenic actions on energy expenditure in female mice.

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Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
Department of Pathology, Harvard Medical School, and Department of Cancer Biology Dana-Farber Cancer Institute, Boston, MA 021151, USA.
Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.


Estrogens 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.

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