Prediction of circulating adipokine levels by body fat compartments and adipose tissue gene expression

Introduction Over the past years, adipose tissue (AT) has been recognized as a metabolically active tissue and a number of AT-derived circulating biomarkers called adipokines have been proposed as mediators for the association of obesity with chronic disease risk. However, the mechanisms are not yet understood and it is even unclear to what extent the amount of subcutaneous (SAT) and visceral adipose tissue (VAT) and gene expression levels in AT predict adipokine concentrations. Methods In the present study, we aimed to assess to what extent adiposity as objectively measured by the amount of SAT and VAT using magnetic resonance imaging, and gene expression levels in SAT, collected by biopsy, determine plasma adipokine concentrations. We investigated the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6 and fatty acid binding protein 4 (FABP4) in a cross-sectional analysis of 200 participants from the population-based EPIC Potsdam cohort study. Our hypothesis was that direct quantification of SAT and VAT as well as gene expression in AT can explain a substantial amount of the variance in adipokine levels, and we calculated the explained variance of plasma adipokines from multivariable regression models. In secondary analyses, we investigated additional predictors (other anthropometric measures, personal characteristics, other gene expression and plasma concentration measures) and also obtained partial correlation coefficients adjusted for age, sex, physical activity and occupational training for a more detailed assessment and comparison of the associations. Results For leptin, 81%, and for FABP4, 45% of the variance in plasma concentrations was explained by SAT and VAT mass, and gene expression in SAT. For the remaining adipokines, AT mass and gene expression explained less than 16% of their variance. Gene expression in SAT explained a smaller proportion of the variance in comparison to AT mass. Regarding the AT compartments, leptin was more strongly correlated with SAT mass (partial correlation r  = 0.81, 95% CI [0.75; 0.86]) than with VAT mass ( r  = 0.58, 95% CI [0.46; 0.67]). For the remaining adipokines, no substantial differences in their correlation with SAT versus VAT mass were observed. The additionally investigated predictors added only little explained variance for some adipokines. Conclusions Our data suggest that except for leptin and FABP4, adiposity as objectively measured by SAT and VAT mass, and gene expression in SAT predict plasma adipokine concentrations only to a small extent. While our findings do not contradict a potential role of adipokines in disease development, the circulating concentrations of all investigated adipokines except leptin and FABP4 are unlikely to mediate the association between adiposity and disease risk observed in epidemiological studies to a large extent.