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Leptin Concentrations in Relation to Body Mass Index and the Tumor Necrosis Factor- System in Humans¹

The Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of the Beth Israel Deaconess Medical Center (C.S.M., S.M., V.K., J.S.F.), Department of Internal Medicine, Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; Department of Propedeutic Medicine (I.A., N.K.), Athens University Medical School, Athens; 401 Military Hospital (A.L., D.E.D., I.G.), Athens, Greece

Address correspondence and requests for reprints to: Jeffrey S. Flier, MD, Division of Endocrinology, RN 325, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Boston, Massachusetts 02215; E-mail: jflier{at}bidmc.harvard.edu

The expression of leptin, an adipocyte-derived protein whose circulating levels reflect energy stores, can be induced by tumor necrosis factor (TNF) in rodents, but an association between the TNF system and leptin levels has not been reported in humans. To evaluate the potential association between serum leptin and the TNF system, we measured the levels of soluble TNF-receptor (sTNF-R55), which has been validated as a sensitive indicator of activation of the TNF system. We studied two groups: 1) 82 young healthy normal controls and 2) 48 patients with noninsulin dependent diabetes mellitus (NIDDM) and 24 appropriately matched controls. By simple regression analysis in controls, there was a strong positive association between leptin and 3 parameters: body mass index, sTNF-R55, and insulin levels. In a multiple regression analysis model, leptin remained significantly and strongly associated with body mass index, and the association of leptin with both insulin and sTNF-R55, although weakened, remained significant. Patients with NIDDM had leptin concentrations similar to controls of similar weight. Importantly, serum levels of sTNF-R55 were also positively and independently associated with leptin in this group of diabetic subjects and matched controls. These data are consistent with the hypothesis that the TNF system plays a role in regulating leptin levels in humans. Further elucidation of a possible role of the TNF system in leptin expression and circulating levels may have important implications for our understanding of obesity and cachexia in humans.

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