FPLD2 LMNA mutation R482W dysregulates iPSC-derived adipocyte function and lipid metabolism.

Lipodystrophies are disorders that directly affect lipid metabolism and storage. Familial partial lipodystrophy type 2 (FPLD2) is caused by an autosomal dominant mutation in the LMNA gene. FPLD2 is characterized by abnormal adipose tissue distribution. This leads to metabolic deficiencies, such as insulin-resistant diabetes mellitus and hypertriglyceridemia. Here we have derived iPSC lines from two individuals diagnosed with FPLD2, and differentiated these cells into adipocytes. Adipogenesis and certain adipocyte functions are impaired in FPLD2-adipocytes. Consistent with the lipodystrophic phenotype, FPLD2-adipocytes appear to accumulate markers of autophagy and catabolize triglycerides at higher levels than control adipocytes. These data are suggestive of a mechanism causing the lack of adipose tissue in FPLD2 patients.