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.


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


METHODS
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.


METHODS
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.
Viardot
Alexander
A
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Sydney-Darlinghurst NSW 2010, Australia. a.viardot@garvan.org.au
Sze
Lisa
L
Purtell
Louise
L
Sainsbury
Amanda
A
Loughnan
Georgina
G
Smith
Ellie
E
Herzog
Herbert
H
Steinbeck
Katharine
K
Campbell
Lesley V
LV
D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000097:blood; D050154:Adiposity / Q000502:physiology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D009765:Obesity / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000150:complications / Q000276:immunology* / Q000378:metabolism
D052242:Adiponectin; D015703:Antigens, CD; D015850:Interleukin-6; D002097:C-Reactive Protein