期刊
CELL METABOLISM
卷 11, 期 4, 页码 286-297出版社
CELL PRESS
DOI: 10.1016/j.cmet.2010.03.002
关键词
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资金
- NIH [1PL10K081182, 1UL1RR024923, 1F32DK066972, K99HD056491, P01 DK56116, R01DK53301, RL1DK081185, TL1DK081181]
- Cancer Biology Fund of the University of Toledo Foundation
- NICHD/NIH [U54-H028934]
- German research foundation [DFG1492-7/1]
- American Diabetes Association
- Smith Family Foundation Pinnacle Program
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) IRflox/flox mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, 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.
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