To assess the individual role of splanchnic organs, kidney, and periph
eral tissues on leptin metabolism, leptin exchange across the splanchn
ic bed, kidney, and leg has been evaluated by the arterio-venous techn
ique in postabsorptive non-obese subjects. Leptin levels in the hepati
c and renal veins were significantly lower (p < 0.001), while femoral
vein levels were consistently greater (p < 0.05) than in the artery. T
he fractional extraction of leptin, namely the percentage of arterial
leptin extracted, was greater in splanchnic organs (16%) than in the k
idney (9.5%). Urinary excretion of leptin was undetectable in most sub
jects, indicating that leptin is degraded within the kidney. There was
no correlation between fractional extraction of leptin and glomerular
filtration rate, whereas leptin fractional extraction was directly re
lated to renal plasma flow (p = 0.017),Renal leptin clearance was abou
t 50% of the glomerular filtration rate. Our data demonstrate that bot
h splanchnic organs and the kidney cooperate in the disposal of leptin
, while peripheral tissues add significant amounts of leptin to the ci
rculation. In non-obese subjects the contribution of the kidney to who
le body clearance is no more than 50%. The removal of leptin by the ki
dney depends on renal plasma flow but not on glomerular filtration rat
e or filtered leptin. (C) 1998 Academic Press.