We determined whether the physiologic changes that accompany food intake or sympathetic activation by beta-adrenergic stimulation result in alterations in the secretion of leptin, tumor necrosis factor-alpha (TNF alpha), or interleukin-6 (IL-6) by serially sampling sc abdominal adipose interstitial fluid by open-flow microperfusion before and after a standardized meal and in response to isoproterenol (1 micromol/L) delivered locally. Post cibum IL-6 rose up to 5-fold, whereas leptin and TNF alpha secretion did not change; TNF alpha, but not IL-6, correlated positively with indices of lipolysis. Isoproterenol-induced lipolysis was accompanied by a transient 40% reduction in leptin and a parallel 85% elevation of TNF alpha concentration, whereas IL-6 levels did not change; again, TNF alpha correlated positively with lipolysis. These data show that secretion of some, but not all, metabolically relevant polypeptides by adipose tissue is modulated within a short time frame by food or stress stimuli, suggesting a role of these peptides in local autocrine/paracrine or distant endocrine effects on fat metabolism. TNF alpha's close correlation with lipolysis suggests that this cytokine participates in a local positive autocrine feedback loop, potentiating lipolysis and inhibiting insulin's antilipolytic actions. The regulations of adipose leptin, TNF alpha, and IL-6 secretion seem distinct from each other and different in the fed vs. fasting state.