Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility

Jennifer W. Hill, Carol F. Elias, Makoto Fukuda, Kevin W. Williams, Eric D. Berglund, William L. Holland, You Ree Cho, Jen Chieh Chuang, Yong Xu, Michelle Choi, Danielle Lauzon, Charlotte E. Lee, Roberto Coppari, James A. Richardson, Jeffrey M. Zigman, Streamson Chua, Philipp E. Scherer, Bradford B. Lowell, Jens C. Brüning, Joel K. Elmquist

Research output: Contribution to journalArticle

233 Scopus citations

Abstract

Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. However, the physiological significance of concomitant leptin and insulin action on POMC neurons remains to be established. Here, we show that mice lacking both leptin and insulin receptors in POMC neurons (Pomc-Cre, Leprflox/flox IRflox/flox mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, Leprflox/flox IRflox/flox female mice display elevated serum testosterone levels and ovarian abnormalities, resulting in reduced fertility. We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function.

Original languageEnglish (US)
Pages (from-to)286-297
Number of pages12
JournalCell metabolism
Volume11
Issue number4
DOIs
StatePublished - Apr 7 2010

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Hill, J. W., Elias, C. F., Fukuda, M., Williams, K. W., Berglund, E. D., Holland, W. L., Cho, Y. R., Chuang, J. C., Xu, Y., Choi, M., Lauzon, D., Lee, C. E., Coppari, R., Richardson, J. A., Zigman, J. M., Chua, S., Scherer, P. E., Lowell, B. B., Brüning, J. C., & Elmquist, J. K. (2010). Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility. Cell metabolism, 11(4), 286-297. https://doi.org/10.1016/j.cmet.2010.03.002