Prader-Willi syndrome is associated with activation of the innate immune system independently of central adiposity and insulin resistance.

BACKGROUND

Subjects with Prader-Willi syndrome (PWS) have a reduced life expectancy due to cardiovascular disease. Increased systemic low-grade inflammation is postulated as a contributor, despite reported lower visceral fat mass and increased insulin sensitivity.

OBJECTIVES

Our aim was to compare inflammatory markers and arterial stiffness in PWS and adiposity-matched obese control subjects.

DESIGN

We conducted a cross-sectional cohort study comparing 12 PWS subjects, 12 obese subjects matched for percentage body fat and central abdominal fat mass, and 10 healthy normal-weight subjects.

MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry was used to assess body composition, flow cytometry to quantify activation markers on immun e cells, and ELISA for measurement of C-reactive protein, adiponectin, and IL-6. Insulin resistance was estimated by homeostasis model assessment and arterial stiffness by applanation tonometry.

RESULTS

PWS and obese subjects had similarly increased homeostasis model assessment and arterial stiffness. Nevertheless, PWS subjects showed significantly higher IL-6 (4.9 + or - 1.0 vs. 2.5 + or - 0.4 pg/ml; P = 0.02) and nonsignificantly higher C-reactive protein (10.5 + or - 3.2 vs. 4.0 + or - 1.0 ng/ml; P = 0.08). Neutrophil activation markers CD66b and CD11b were higher in PWS compared to obese subjects (P < 0.01), reflecting an activated innate immune system. These markers were positively related to central adiposity in lean and obese subjects (r = 0.49; P < 0.05), but not in PWS subjects.

CONCLUSIONS

PWS subjects compared to adiposity-matched obese subjects demonstrate similar insulin resistance but increased low-grade inflammation. The dissociation of inflammation and central adiposity suggests that activation of innate immunity may be either a specific genetic feature of PWS or linked to the commonly associated obstructive sleep apnea syndrome, and might offer a treatment target to reduce cardiovascular disease.