The objective of this study was to determine whether obese human adipose ti
ssue contains preformed stores of leptin and their relationship to secreted
leptin. Detergent increased detectable leptin by about twofold, suggesting
that leptin is stored in a membrane-bound location. Subcutaneous tissue le
ptin was similar to1.6-fold higher than omental, paralleling known differen
ces in leptin secretion and expression. The amount of leptin secreted durin
g a 3-h incubation was similar to that of extractable tissue leptin. Tissue
leptin levels were maintained over the incubation. Inhibition of protein s
ynthesis decreased tissue leptin content but did not decrease leptin secret
ion until after 3 h of incubation. Culture of adipose tissue for 2 days wit
h the combination of insulin and dexamethasone, but not with either hormone
alone, increased tissue leptin content about twofold in both depots. Altho
ugh insulin did not affect tissue leptin content, it potentiated leptin sec
retion (as a % of tissue stores). These data suggest that adipose tissue le
ptin storage and secretion per se are regulated. Regulation of the release
of preformed leptin may modulate serum leptin levels in obese humans.