Document Detail


Prader-Willi syndrome is associated with activation of the innate immune system independently of central adiposity and insulin resistance.
MedLine Citation:
PMID:  20444923     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Alexander Viardot; Lisa Sze; Louise Purtell; Amanda Sainsbury; Georgina Loughnan; Ellie Smith; Herbert Herzog; Katharine Steinbeck; Lesley V Campbell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-05
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-07-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3392-9     Citation Subset:  AIM; IM    
Affiliation:
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Sydney-Darlinghurst NSW 2010, Australia. a.viardot@garvan.org.au
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MeSH Terms
Descriptor/Qualifier:
Absorptiometry, Photon
Adiponectin / blood
Adiposity / physiology*
Antigens, CD / immunology,  metabolism
C-Reactive Protein / metabolism
Cohort Studies
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Immunity, Innate / physiology*
Insulin Resistance / physiology*
Interleukin-6 / blood
Obesity / complications,  immunology*,  metabolism
Prader-Willi Syndrome / complications,  immunology*,  metabolism
Chemical
Reg. No./Substance:
0/Adiponectin; 0/Antigens, CD; 0/Interleukin-6; 9007-41-4/C-Reactive Protein

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