Institut National de la Santé et de la Recherche Médicale, Unité 938, University Pierre and Marie Curie, Faculté de Médecine Pierre et Marie Curie, Site Saint-Antoine, 27 Rue Chaligny, 75012 Paris France.
J Clin Endocrinol Metab. 2010 Mar;95(3):1463-8. doi: 10.1210/jc.2009-1824. Epub 2010 Jan 22.
Human lipodystrophies are characterized by loss of adipose tissue, insulin resistance, and metabolic complications. The mechanisms linking fat loss to severe insulin resistance remain unclear. Adipokines may have important roles as intermediary players in metabolism.
We sought to determine the plasma concentrations of leptin and adiponectin in patients with Berardinelli-Seip congenital lipodystrophy (BSCL) harboring mutations in the genes encoding either 1-acylglycerol-3-phosphate-O-acyltransferase-2 (AGPAT2) or BSCL2/seipin, in comparison with patients with other forms of inherited or acquired lipodystrophies or insulin receptor alterations.
Leptin and total and high-molecular-weight adiponectin were measured in plasma of 16 BSCL1/AGPAT2 and 19 BSCL2/seipin patients and compared with heterozygous (n = 22) or nonmutated relatives (controls, n = 30); patients with Dunnigan-type partial lipodystrophy due to lamin A/C mutations (n = 23), HIV-related lipodystrophy (n = 124), and insulin receptor dysfunctions caused by mutations or autoantibodies (n = 17).
Leptin was dramatically decreased in BSCL patients as compared with other subgroups. Adiponectin was decreased in BSCL as compared with controls and patients with altered insulin receptor but was discrepant between the two BSCL subgroups. Whereas total and high-molecular-weight adiponectin levels were almost undetectable in BSCL1/AGPAT2 patients, higher levels were detected in BSCL2/seipin patients, comparable with those of patients with partial lipodystrophy. Adiponectin greater than 1.6 mg/liter had a 100% negative predictive value for AGPAT2 mutations in inherited lipodystrophies.
The presence of circulating adiponectin in BSCL2/seipin patients with near absence of adipose tissue outlines the complexity of adiponectin biology. Use of circulating adiponectin might be helpful to guide the genetic investigations in BSCL.
人体脂肪营养不良的特征是脂肪组织丧失、胰岛素抵抗和代谢并发症。将脂肪丧失与严重胰岛素抵抗联系起来的机制尚不清楚。脂肪细胞因子可能在代谢中作为中介因子发挥重要作用。
我们试图确定携带编码 1-酰基甘油-3-磷酸-O-酰基转移酶-2（AGPAT2）或 BSCL2/seipin 基因突变的 Berardinelli-Seip 先天性脂肪营养不良（BSCL）患者与其他遗传性或获得性脂肪营养不良或胰岛素受体改变患者的血浆瘦素和脂联素浓度。
测量了 16 名 BSCL1/AGPAT2 和 19 名 BSCL2/seipin 患者的血浆瘦素和总及高分子量脂联素，并与杂合子（n=22）或非突变亲属（对照组，n=30）；由于 lamin A/C 突变导致的 Dunnigan 型部分脂肪营养不良患者（n=23）、HIV 相关脂肪营养不良患者（n=124）和因突变或自身抗体导致的胰岛素受体功能障碍患者（n=17）。
与其他亚组相比，BSCL 患者的瘦素显著降低。与对照组和胰岛素受体改变患者相比，BSCL 患者的脂联素降低，但在两个 BSCL 亚组之间存在差异。BSCL1/AGPAT2 患者的总及高分子量脂联素水平几乎无法检测到，而 BSCL2/seipin 患者的水平较高，与部分脂肪营养不良患者相当。脂联素大于 1.6mg/L 对遗传性脂肪营养不良中 AGPAT2 突变具有 100%的阴性预测值。
BSCL2/seipin 患者存在循环脂联素，而其脂肪组织几乎不存在，这突出了脂联素生物学的复杂性。循环脂联素的使用可能有助于指导 BSCL 的基因研究。
