Leptin is released from the human brain: Influence of adiposity and gender

Leptin, a 16-kDa circulating protein primarily derived from adipocytes, is an important factor in the regulation of appetite and energy expenditure. U sing simultaneous arterio-venous blood sampling, several organs were assess ed with regard to their individual roles in leptin metabolism in healthy ma le and female subjects constituting a range of body mass indices. Plasma le ptin levels were unchanged after passage through the hepatosplanchnic and f orearm circulations. In contrast, concentrations in the renal vein were con sistently lower than those in the renal artery (-15%; P < 0.005), indicatin g net extraction, whereas the brain was observed to be a net leptin release r. Concentrations in the internal jugular vein were significantly higher th an arterial levels in lean females (change, 3.0 +/- 1.2 ng/mL; P < 0.02) an d in obese males (body mass index, >28 kg/m(2)), but not lean (change, 2.3 +/- 2.3 vs. 0.1 +/- 0.1 ng/mL, respectively; P < 0.05), indicating a probab le influence of both gender and adiposity on brain leptin release. An attem pt to grossly localize the site of brain release by using cerebral venous s cans to distinguish between jugular venous drainage from cortical and subco rtical brain areas revealed no region-specific secretion. These data raise the possibility that the brain is a nonadipose source of leptin. In additio n, the higher level of brain release observed in females may contribute to the well documented gender differences in overall plasma leptin levels.