ABSTRACT
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.
Subject(s)
Bardet-Biedl Syndrome/blood , Leptin/blood , Leptin/physiology , Absorptiometry, Photon , Adiposity/genetics , Adiposity/physiology , Adolescent , Adult , Bardet-Biedl Syndrome/genetics , Blood Glucose/metabolism , Blood Pressure/physiology , Body Composition/genetics , Body Composition/physiology , Body Height/physiology , Body Mass Index , Child , Child, Preschool , DNA/genetics , Female , Humans , Insulin/blood , Insulin Resistance/physiology , Leptin/genetics , Male , Middle Aged , Mutation/genetics , Obesity/blood , Obesity/genetics , Reverse Transcriptase Polymerase Chain Reaction , Triglycerides/blood , Young AdultABSTRACT
Polyploidy, or genome doubling, is a common mechanism in the evolution of plants. This genome duplication can rapidly lead to genomic changes between ploidy levels. In particular, allopolyploids that result from interspecific hybridization can show a large number of changes in gene expression immediately after the polyploidy event. These are likely due to epigenetic changes that do not alter the underlying DNA sequence. This may be due in part to the hybrid origin of these allopolyploids. In autopolyploids, a small number of studies have shown that there may also be some gene expression changes between ploidy levels, albeit to a much smaller degree. However, these studies have focused on inbred lines of single populations. This study examines silencing and/or novel gene expression in diploid, autotetraploid, and autohexaploid lineages of Helianthus decapetalus. Using cDNA-amplified fragment length polymorphism, we examined gene expression in 5 populations of these lineages. The results show no ploidy level-specific differences in gene silencing or novel gene expression. All gene expression differences are among populations and may be due to independent evolutionary origins. These results support the conclusions of previous studies that gene expression differences among allopolyploids are likely due in large part to the hybrid nature of these lineages.
