Type 2 familial partial lipodystrophy (FPLD2) is characterized by loss of fat in the limbs and buttocks and results from mutations in the LMNA gene. The aim of this study was to evaluate the role of several genes involved in adipogenesis in order to better understand the underlying mechanisms of regional loss of subcutaneous adipose tissue (scAT) in patients with FPLD2. Subjects and Methods: Seven patients with FPLD2 and ten control healthy subjects were studied. Minimal model was used to calculate the insulin sensitivity (IS).. scAT was obtained from abdomen and thigh by biopsy. Relative gene expression was quantified by real time RT-PCR in a Light Cycler 2.0. Prelamin A western blot analysis was carried out on scAT. Prelamin A nuclear localisation was determined using immunofluorescence. Adipocyte nuclei were examined by electron microscopy. Results: Patients with FPLD2 were found to have significantly lower IS. The expression of LMNA was similar in both groups. The expression of PPARG2, RB1, CCND3 and LPL, in thigh, but not in abdomen scAT, was significantly reduced (67%, 25%, 38% and 66% respectively) in FPLD2 patients. Significantly higher levels of prelamin A were detected in peripheral scAT of FPLD2 patients. Defects in the peripheral heterochromatin and a nuclear fibrous dense lamina were present in adipocytes of FPLD2 patients. Conclusions: In FPLD2 subjects, prelamin A accumulation in peripheral scAT is associated with a reduced expression of several genes involved in adipogenesis, which could perturb the balance between proliferation and differentiation in adipocytes leading to less efficient tissue regeneration.
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