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The Differential Effect of Food Intake and ß-Adrenergic Stimulation on Adipose-Derived Hormones and Cytokines in Man

Developmental Endocrinology Branch (Z.O., G.P.C.), National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland 20892; Clinical Pathology Department (A.T.R., M.S.), National Institutes of Health, Bethesda, Maryland 20892; and Institute of Biomedical Engineering (Z.T.), Graz University of Technology, 8010 Graz, Austria

Address all correspondence and requests for reprints to: Zsolt Orban, M.D., Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10, Room 10N262, 10 Center Drive, Bethesda, Maryland 20892-1862. E-mail: orbanz{at}cc1.nichd.nih.gov

We determined whether the physiologic changes that accompany food intake or sympathetic activation by ß-adrenergic stimulation result in alterations in the secretion of leptin, tumor necrosis factor- (TNF), 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 µmol/L) delivered locally. Post cibum IL-6 rose up to 5-fold, whereas leptin and TNF secretion did not change; TNF, 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 concentration, whereas IL-6 levels did not change; again, TNF 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’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, and IL-6 secretion seem distinct from each other and different in the fed vs. fasting state.

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