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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Weight
  • Disease Models, Animal
  • Energy Metabolism
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / metabolism*
  • Estrogens / pharmacology
  • Female
  • Male
  • Mice
  • Obesity / chemically induced
  • Obesity / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Sex Characteristics
  • Ventromedial Hypothalamic Nucleus / metabolism*

Substances

  • Estrogen Receptor alpha
  • Estrogens
  • Phosphatidylinositol 3-Kinases