Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-4472, USA.
J Clin Endocrinol Metab. 2011 Mar;96(3):E528-35. doi: 10.1210/jc.2010-2290. Epub 2011 Jan 5.
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.
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.
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.
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.
Bardet-Biedl 综合征（BBS）是一种与肥胖相关的原发性纤毛遗传异质性疾病。在 BBS 小鼠模型中，纤毛功能障碍导致肥胖前瘦素信号转导受损和高瘦素血症。为了研究 BBS 肥胖的病理生理学，我们比较了 BBS 患者和体重指数 Z 评分（BMI-Z）匹配的对照组。
将 50 名 BBS 患者按年龄、性别、种族和 BMI-Z 与 100 名对照者 2:1 匹配。比较 BBS 患者和对照组在体成分（双能 X 射线吸收法、腹部磁共振成像）、血压 Z 评分（BP-Z；按年龄、性别和身高标准化）以及空腹瘦素、血脂、胰岛素和血糖浓度方面的差异。还比较了 BBS 患者的基因型。
与对照组相比，BBS 患者的瘦素、甘油三酯、腹内脂肪量和舒张压 Z 评分显著更高。BBS1（27%）和 BBS10（30%）突变最为常见。BBS10 突变患者的 BMI-Z 更高、内脏脂肪量更大、胰岛素抵抗更严重，而 BBS1 突变患者则更低。
BBS 患者的瘦素水平高于其肥胖程度预期，这与纤毛病导致的瘦素信号转导功能障碍与瘦素抵抗有关的观点一致。BBS 患者腹部脂肪的优先沉积可能表明存在代谢并发症的倾向，包括高血压和高三酰甘油血症。BBS10 与 BBS1 突变组之间观察到的不同结果是首次证明不同基因突变导致 BBS 患者存在生理差异。这些结果表明，BBS 的肥胖与非综合征性肥胖不同。
