LEPTIN CONCENTRATIONS IN RELATION TO BODY-MASS INDEX AND THE TUMOR-NECROSIS-FACTOR-ALPHA SYSTEM IN HUMANS

The expression of leptin, an adipocyte-derived protein whose circulati ng levels reflect energy stores, can be induced by tumor necrosis fact or (TNF)alpha in rodents, but an association between the TNF alpha sys tem and leptin levels has not been reported in humans. To evaluate the potential association between serum leptin and the TNF alpha system, we measured the levels of soluble TNF alpha-receptor (sTNF alpha-R55), which has been validated as a sensitive indicator of activation of th e TNF alpha system. We studied two groups: 1) 82 young healthy normal controls and 2) 48 patients with noninsulin dependent diabetes mellitu s (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 alpha-R55, and insulin levels. In a multiple regression analysis model, leptin remained signi ficantly and strongly associated with body mass index, and the associa tion of leptin with both insulin and sTNF alpha-R55, although weakened , remained significant. Patients with NIDDM had leptin concentrations similar to controls of similar weight. Importantly, serum levels of sT NF alpha-R55 were also positively and independently associated with le ptin in this group of diabetic subjects and matched controls. These da ta are consistent with the hypothesis that the TNF alpha system plays a role in regulating leptin levels in humans. Further elucidation of a possible role of the TNF alpha system in leptin expression and circul ating levels may have important implications for our understanding of obesity and cachexia in humans.