[PDF][PDF] Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility

JW Hill, CF Elias, M Fukuda, KW Williams, ED Berglund… - Cell metabolism, 2010 - cell.com
JW Hill, CF Elias, M Fukuda, KW Williams, ED Berglund, WL Holland, YR Cho, JC Chuang
Cell metabolism, 2010cell.com
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 …
Summary
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.
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