UPMC Univ Paris 06, UMR_S938, Paris, France.
Am J Pathol. 2011 Nov;179(5):2443-53. doi: 10.1016/j.ajpath.2011.07.049. Epub 2011 Sep 21.
Some LMNA mutations responsible for insulin-resistant lipodystrophic syndromes are associated with peripheral subcutaneous lipoatrophy and faciocervical fat accumulation. Their pathophysiologic characteristics are unknown. We compared histologic, immunohistologic, ultrastructural, and protein expression features of enlarged cervical subcutaneous adipose tissue (scAT) obtained during plastic surgery from four patients with LMNA p.R482W, p.R439C, or p.H506D mutations versus cervical fat from eight control subjects, buffalo humps from five patients with HIV infection treated or not with protease inhibitors, and dorsocervical lipomas from two patients with mitochondrial DNA mutations. LMNA-mutated cervical scAT and HIV-related buffalo humps were dystrophic, with an increased percentage of small adipocytes, increased fibrosis without inflammatory features, and decreased number of blood vessels, as compared with control samples. Samples from patients with LMNA mutations or protease inhibitor-based therapy demonstrated accumulation of prelamin A, altered expression of adipogenic proteins and brown fat-like features, with an increased number of mitochondria and overexpression of uncoupling protein 1 (UCP1). These features were absent in samples from control subjects and from patients with HIV not treated with protease inhibitors. Mitochondrial DNA-mutated cervical lipomas demonstrated inflammatory fibrosis with distinct mitochondrial abnormalities but neither UCP1 expression nor prelamin A accumulation. In conclusion, Enlarged cervical scAT from patients with lipodystrophy demonstrated small adipocytes, fibrosis, and decreased vessel numbers. However, only cervical fat from patients with LMNA mutations or who had received protease inhibitor therapy accumulated prelamin A and exhibited similar remodeling toward a brown-like phenotype with UCP1 overexpression and mitochondrial alterations.
一些导致胰岛素抵抗性脂肪营养不良综合征的 LMNA 突变与周围皮下脂肪萎缩和面颈部脂肪堆积有关。其病理生理特征尚不清楚。我们比较了四名携带 LMNA p.R482W、p.R439C 或 p.H506D 突变的患者在整形手术中获得的增大的颈皮下脂肪组织 (scAT) 的组织学、免疫组织化学、超微结构和蛋白表达特征，以及 8 名对照者、5 名接受或未接受蛋白酶抑制剂治疗的 HIV 感染患者的水牛肩和 2 名携带线粒体 DNA 突变患者的背颈部脂肪瘤的颈脂肪。与对照样本相比，LMNA 突变相关的颈 scAT 和 HIV 相关的水牛肩表现为营养不良，小脂肪细胞比例增加，纤维化无炎症特征，血管数量减少。来自携带 LMNA 突变或基于蛋白酶抑制剂治疗的患者的样本表现出前层粘连蛋白 A 的积累、脂肪生成蛋白表达的改变和棕色脂肪样特征，伴随着线粒体数量的增加和解偶联蛋白 1 (UCP1) 的过度表达。这些特征在对照样本和未接受蛋白酶抑制剂治疗的 HIV 患者的样本中均不存在。携带线粒体 DNA 突变的颈脂肪瘤表现出炎症性纤维化，伴有明显的线粒体异常，但无 UCP1 表达或前层粘连蛋白 A 积累。总之，脂肪营养不良患者的增大颈 scAT 表现为小脂肪细胞、纤维化和血管数量减少。然而，只有携带 LMNA 突变或接受蛋白酶抑制剂治疗的患者的颈脂肪才会积累前层粘连蛋白 A，并表现出类似的重塑，表现为 UCP1 过表达和线粒体改变的棕色样表型。
