SAT-106 Plasma Interleukine-6 (IL-6) Concentration Is a Determinant of Free-Living Weight Change in Healthy Humans

Background: IL-6 is a multifunctional cytokine secreted by leukocytes and endothelial cells in multiple organs. Mice with IL-6 deficiency show mature-onset obesity due to decreased energy expenditure (EE) but no change in food intake. In humans, IL-6 concentration increases with obesity; however, the causal relationship with future weight gain is unclear. We investigated if fasting plasma IL-6 concentration predicts weight change in lean and overweight individuals. Methods: While residing in our clinical research unit, forty-nine healthy, weight-stable volunteers (37.5±10.8 y, 26.7±4.0 kg/m(2)BMI, 29.7±9.1% body fat; mean±SD, 39 men) with normal glucose regulation had 24-h EE measurements in a whole-room indirect calorimeter during energy balance and consuming a standard diet (50% carbohydrate, 20% protein). After at least 3 days on weight-maintaining diet and an overnight fast, plasma was collected for measurement of IL-6 concentrations by ELISA (Enzo Life Sciences, Farmingdale, NY; intra-assay CV=7.9%, inter-assay CV=10.5%, range=1.52-50 pg/mL) on 6 different days with values averaged to increase precision. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition. Volunteers returned for follow up assessment of body weight and composition by DXA after 6 months (n=38) and 1 year (n=32). Results: Fasting IL-6 concentrations (geometric mean, 95% CI: 11.5, 10.0-13.2 pg/mL) did not differ by gender or race (p>0.05) nor were associated with age, BMI, % body fat, fat mass (FM), or fat-free mass (FFM). After adjustment for body composition and other known EE determinants, fasting IL-6 concentration was not associated with 24-h EE (p=0.33), sleeping EE (p=0.85), or respiratory quotient (p=0.76). However, higher IL-6 concentration was associated with weight gain at 6 months (r=0.51, p=0.001) and at 1 year (r=0.45, p=0.009), reflecting increases in FM (r=0.42, p=0.01 and r=0.50, p=0.04, respectively), but not FFM (p=0.09 and p=0.40). In a linear model, fasting IL-6 concentration at baseline was an independent predictor of weight gain at 6 months and 1 year [β=13.2 (95% CI: 5.7-20.8) and 15.1 kg (1.6-28.7) per 10-fold increase, p=0.001 and 0.03; respectively] after accounting for baseline weight, age, and sex. Conclusion: Although not influencing EE, higher plasma concentration of IL-6 predicts future weight and FM gain in humans, suggesting a potentially novel role of IL-6 in food intake and overeating.