Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, University of Santiago de Compostela, Spain.
Clin Endocrinol (Oxf). 2012 Jun;76(6):816-24. doi: 10.1111/j.1365-2265.2011.04208.x.
Type 2 familial partial lipodystrophy (FPLD2) is a rare adipose tissue (AT) disease caused by mutations in LMNA, in which lipomas appear occasionally. In this study, we aimed to histologically characterize FPLD2-associated lipomatosis and study the expression of genes and proteins involved in cell cycle control, mitochondrial function, inflammation and adipogenesis.
One lipoma and perilipoma fat from each of four subjects with FPLD2 and 10 control subjects were analysed by optical microscopy. The presence of inflammatory cells was evaluated by immunohistochemistry. Real-time RT-PCR and Western blot were used to evaluate gene and protein levels.
Adipocytes from lipodystrophic patients were significantly larger than those of controls, in both the lipomas and perilipoma fat. Lipodystrophic AT exhibited CD68(+) macrophages and CD3(+) lymphocytes infiltration. TP53 expression was reduced in all types of lipomas. At protein level, C/EBPβ, p53 and pRb were severely disturbed in both lipodystrophic lipomas and perilipoma fat coming from lipoatrophic areas, whereas the expression of CEBPα was normal. Mitochondrial function genes were less expressed in lipoatrophic fat. In both lipomas and perilipoma fat from lipoatrophic areas, the expression of adipogenes was lower than controls.
Even in lipomas, the adipogenic machinery is impaired in lipodystrophic fat coming from lipoatrophic regions in FPLD2, although the histological phenotype is near-normal, exhibiting low-grade inflammatory features. Our results suggest that the p53 pathway and some adipogenic proteins, such as CEBPα, could contribute to the maintenance of this near normal phenotype in the remnant AT present in these patients.
2 型家族性部分脂肪营养不良（FPLD2）是一种罕见的脂肪组织（AT）疾病，由 LMNA 突变引起，偶尔会出现脂肪瘤。在这项研究中，我们旨在从组织学上描述 FPLD2 相关的脂肪增生，并研究涉及细胞周期控制、线粒体功能、炎症和脂肪生成的基因和蛋白的表达。
分析了 4 名 FPLD2 患者的每个脂肪瘤和脂肪瘤脂肪，以及 10 名对照者的每个脂肪样本，通过光学显微镜。通过免疫组织化学评估炎症细胞的存在。实时 RT-PCR 和 Western blot 用于评估基因和蛋白水平。
与对照组相比，脂肪营养不良患者的脂肪细胞在脂肪瘤和脂肪瘤脂肪中均明显增大。脂肪营养不良的 AT 表现为 CD68（+）巨噬细胞和 CD3（+）淋巴细胞浸润。所有类型的脂肪瘤中 TP53 表达均降低。在脂肪营养不良的脂肪瘤和来自脂肪萎缩区的脂肪瘤脂肪中，C/EBPβ、p53 和 pRb 蛋白水平严重紊乱，而 CEBPα 的表达正常。脂肪萎缩脂肪中，线粒体功能基因表达减少。在来自脂肪萎缩区的脂肪瘤和脂肪瘤脂肪中，脂肪生成基因的表达均低于对照组。
即使在脂肪瘤中，来自 FPLD2 脂肪萎缩区的脂肪营养不良脂肪中的脂肪生成机制受损，尽管组织学表型接近正常，表现出低度炎症特征。我们的结果表明，p53 通路和一些脂肪生成蛋白，如 CEBPα，可能有助于维持这些患者剩余 AT 的这种接近正常表型。
