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Publication : Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility.

First Author  Hill JW Year  2010
Journal  Cell Metab Volume  11
Issue  4 Pages  286-97
PubMed ID  20374961 Mgi Jnum  J:159615
Mgi Id  MGI:4452165 Doi  10.1016/j.cmet.2010.03.002
Citation  Hill JW, et al. (2010) Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab 11(4):286-97
abstractText  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, Lepr(flox/flox) IR(flox/flox) mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, Lepr(flox/flox) IR(flox/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.
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