Histological and molecular features of lipomatous and nonlipomatous adipose tissue in familial partial lipodystrophy caused by LMNA mutations

Objectives 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. Design and patients 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. Results 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/EBP beta, p53 and pRb were severely disturbed in both lipodystrophic lipomas and perilipoma fat coming from lipoatrophic areas, whereas the expression of CEBPa 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. Conclusions 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 CEBPa, could contribute to the maintenance of this near normal phenotype in the remnant AT present in these patients.