Altered expression of master regulatory genes of adipogenesis in lipomas from patients bearing tRNALys point mutations in mitochondrial DNA

The mechanisms underlying the appearance of lipomas in patients bearing mutations in the tRNA(Lys) gene of mitochondrial DNA are unknown. We investigated changes in gene expression patterns in lipomas from three patients bearing A8344G or G8363A tRNA(Lys) gene mutations. Uncoupling protein-1 mRNA was detected in the lipomas, in contrast with undetectable expression in normal adipose tissue. However, expression of other markers of brown fat, such as PGC-1 alpha, was unaltered. PPAR gamma and retinoblastoma gene expression was down regulated in the lipomas, but C/EBP alpha mRNA was not affected. The expression of Pref-1 was dramatically down regulated. Thus, lipomatosis due to tRNALys mutations is associated with a pattern of altered expression of master regulators of adipogenesis consistent with enhanced proliferation but maintenance of adipocyte features, and with a distorted pattern of brown versus white adipocyte differentiation. (c) 2006 Elsevier Inc. All rights reserved.