Document Detail

Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance.
MedLine Citation:
PMID:  21209035     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder of the primary cilium associated with obesity. In BBS mouse models, ciliary dysfunction leads to impaired leptin signaling and hyperleptinemia before obesity onset. To study the pathophysiology of obesity in BBS, we compared patients with BBS and body mass index Z-score (BMI-Z)-matched controls.
DESIGN AND METHODS: Fifty patients with BBS were matched 2:1 by age, sex, race, and BMI-Z with 100 controls. Patients with BBS and controls were compared for differences in body composition (dual-energy x-ray absorptiometry, abdominal magnetic resonance imaging), blood pressure Z-score (BP-Z; standardized for age, sex, and height), and fasting concentrations of leptin, lipids, insulin, and glucose. Patients with BBS were also compared by genotype.
RESULTS: Leptin, triglycerides, intraabdominal fat mass, and diastolic BP-Z were significantly greater in patients with BBS than in the controls. BBS1 (27%) and BBS10 (30%) mutations were the most prevalent. Patients with BBS10 mutations had significantly higher BMI-Z, greater visceral adiposity, and greater insulin resistance than those with BBS1 mutations.
CONCLUSIONS: Patients with BBS had higher leptin than expected for their degree of adiposity, consistent with the notion that ciliopathy-induced leptin signaling dysfunction is associated with leptin resistance. The preferential deposition of fat intraabdominally in patients with BBS may indicate a predisposition for metabolic complications, including hypertension and hypertriglyceridemia. The observation of disparate results in the BBS10 vs. BBS1 mutation groups is the first demonstration of physiological differences among patients with BBS caused by mutations in distinct genes. These results suggest that the obesity of BBS is distinct from nonsyndromic obesity.
Penelope P Feuillan; David Ng; Joan C Han; Julie C Sapp; Katie Wetsch; Emma Spaulding; Yuqian C Zheng; Rafael C Caruso; Brian P Brooks; Jennifer J Johnston; Jack A Yanovski; Leslie G Biesecker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2011-01-05
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  96     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-07     Completed Date:  2011-05-23     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E528-35     Citation Subset:  AIM; IM    
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-4472, USA.
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MeSH Terms
Absorptiometry, Photon
Adiposity / genetics,  physiology
Bardet-Biedl Syndrome / blood*,  genetics
Blood Glucose / metabolism
Blood Pressure / physiology
Body Composition / genetics,  physiology
Body Height / physiology
Body Mass Index
Child, Preschool
DNA / genetics
Insulin / blood
Insulin Resistance / physiology
Leptin / blood*,  genetics,  physiology*
Middle Aged
Mutation / genetics
Obesity / blood,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Triglycerides / blood
Young Adult
Reg. No./Substance:
0/Blood Glucose; 0/Insulin; 0/Leptin; 0/Triglycerides; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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