Andrea M. Haqq^1,2, Michael J. Muehlbauer²,  Christopher B. Newgard², Laura P. Svetkey^2,3,  Steven C. Grambow^4,5 and Michael S. Freemark¹

Department of Pediatrics¹; Sarah W. Stedman Nutrition and Metabolism Center²; Department of Medicine, Division of Nephrology³; Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center⁴; and Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC⁵

Introduction: Obesity predisposes to co-morbidities including cardiovascular disease, insulin resistance and type 2 diabetes. Adipocytokines released by adipose tissue influence glucose transport/utilization and endothelial function, providing a mechanistic link between obesity and the development of metabolic co-morbidities. Recent studies from our group have found that obese children and adolescents with PWS have lower HOMA-IR and higher adiponectin than BMI-matched controls, suggesting an increase in insulin sensitivity. We hypothesized that differences in plasma adipocytokines might explain, in part, the differences in insulin sensitivity between PWS children and BMI-matched obese controls. The aim of this study, therefore, was to determine the adipocytokine profiles of obese children with PWS compared to non-PWS BMI-matched obese control subjects (OC) and lean subjects (LC).

Methods: 14 children with PWS, 14 BMI-matched obese control subjects (OC) and 14 Lean control (LC) subjects of similar age and gender were studied. Fasting plasma cytokines (TNFa, IL-10, IL-6, IL-1b, IL-2, IL-12p40, IL-8, IL-18, MCP-1, plasminogen activator inhibitor-1 (PAI-1), IFNg, IL-12p70 and Resistin) were measured via multiplex chemiluminescent assay using a Searchlight Plus CCD imager (Pierce Biotechnology, Woburn, MA). Fasting serum high sensitivity C reactive protein (CRP), free (non-esterified) fatty acids (FFA), total cholesterol, HDL, LDL, and triglycerides were performed using a Hitachi 911 auto-analyzer.  Reagents for FFA were supplied by Wako Chemical USA (Richmond, VA), and for the remaining analytes by Roche Diagnostics (Indianapolis, IN). 

Results/Discussion: Baseline characteristics and adipocytokine and lipid profiles are summarized in Table 1. Plasma IL-6 concentrations were lower (p<0.05) in PWS than in BMI-matched obese controls (OC), and plasma IL-1b and IL-12p70 were lower (p<0.05) in PWS than in LC. Plasma PAI-1 concentrations were higher (p<0.05) in PWS and OC compared to LC. Serum CRP was higher (p<0.05) in OC compared to LC, but CRP levels in PWS did not differ significantly from lean subjects.  Plasma TNF-a, IL-10, IL-2, IL-12p40, IL-8, IFNg, IL-18, MCP-1 and serum resistin did not differ between the 3 groups. All 3 groups (PWS, OC, LC) showed similar fasting concentrations of serum cholesterol, LDL, and non-esterified fatty acids. BMI-matched obese controls (OC) had lower HDL and higher triglycerides (TG) than lean subjects (p<0.05), but HDL and TG concentrations in PWS did not differ significantly from those in lean subjects.

Conclusion: The heightened insulin sensitivity of PWS is associated with a trend towards relatively lower IL-6, IL-1b and CRP levels and higher HDL levels and lower TG levels than those in BMI-matched obese controls. This suggests that differences in plasma adipocytokines might explain, in part, the relatively high insulin sensitivity demonstrated in PWS children.

Table 1

All data reported as Medians (25^th , 75^th percentile); *Kruskal-Wallis One Way Analysis of Variance on Ranks used for between group comparisons

Edited: 02/09/2012