As it does with appetite, leptin also influences glucose metabolism. Aberrant glucose metabolism causes the hypergylcemia (high blood-sugar levels) that is the hallmark of diabetes. "There had been considerable controversy as to whether leptin controls glucose metabolism through STAT3 production or not," says Dr. Rossetti. "Using our technique for blocking STAT3, we were able to show that STAT3 is absolutely necessary for the acute effect of leptin on glucose metabolism."

Leptin is also known to influence fertility. Women with very little body fat--elite female athletes, for example--may stop menstruating and experience temporary infertility. This is largely due to inadequate secretion of leutenizing hormone and follicle stimulating hormone by the pituitary gland--which in turn is caused by the near-disappearance of leptin from the bloodstream. A recent study showed that low doses of leptin can restore the menstrual cycle in such women. Using their STAT3-blocking technique, the Einstein researchers showed that this acute effect of leptin depends on the activation of STAT3.

"This work has shown that STAT3 is fundamentally important for expressing several of leptin's acute effects," says Dr. Rossetti. "Since we now fully appreciate the important role of STAT3 in leptin's metabolic actions, strategies designed to restore the effects of leptin on STAT3 should achieve considerable health benefits. An obvious target is obesity, where the big problem is leptin resistance. But in addition, our findings suggest that selectively turning on STAT3 may help prevent diabetes by improving glucose metabolism and help restore fertility as well."

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Contact: Karen Gardner
kgardner@aecom.yu.edu
718-430-3101
Albert Einstein College of Medicine
5-Jul-2006