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 immune 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 +/- 1.0 vs. 2.5 +/- 0.4 pg/ml; P = 0.02) and nonsignificantly higher C-reactive protein (10.5 +/- 3.2 vs. 4.0 +/- 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.
|ISBN||1945-7197 (Electronic) 0021-972X (Linking)|
|Authors||Viardot, A.; Sze, L.; Purtell, L.; Sainsbury, A.; Loughnan, G.; Smith, E.; Herzog, H.; Steinbeck, K.; Campbell, L. V.;|
|Publisher Name||JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM|
|Published Date||2010-01-01 00:00:00|