Fasting, but not adrenalectomy, reduces transport of leptin into the brain.

Food deprivation and adrenalectomy are associated with low concentrations of leptin in blood and the absence of obesity. Because leptin is known to cross the blood-brain barrier (BBB) by a saturable transport system, we examined whether fasting and adrenalectomy (ADX) also act at the BBB. Multiple-time regression analysis showed that fasting, but not ADX, significantly decreased the entry of leptin into mouse brain. After 3 days of food deprivation, the influx of leptin became indistinguishable from that of the vascular control (albumin); 5 h of refeeding significantly reversed this reduced rate of influx. Thus, the results indicate that the BBB provides a dynamic site for the regulation of physiological processes involving leptin.