title: PI3K in the ventromedial hypothalamic nucleus mediates estrogenic actions on energy expenditure in female mice.
abstract: 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.
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: He
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Liangru
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Pingwen
authors.initials: P
authors.lastname: Xu
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Antentor Othrell
authors.initials: AO
authors.lastname: Hinton
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pathology, Harvard Medical School, and Department of Cancer Biology Dana-Farber Cancer Institute, Boston, MA 021151, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Clegg
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004734:Energy Metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012727:Sex Characteristics; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D019869:Phosphatidylinositol 3-Kinases