title: Altered expression of master regulatory genes of adipogenesis in lipomas from patients bearing tRNA(Lys) point mutations in mitochondrial DNA.
abstract: 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-1alpha, was unaltered. PPARgamma and retinoblastoma gene expression was down regulated in the lipomas, but C/EBPalpha mRNA was not affected. The expression of Pref-1 was dramatically down regulated. Thus, lipomatosis due to tRNA(Lys) 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.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Spain.
authors.forename: Jordi P
authors.initials: JP
authors.lastname: Guallar
authors.forename: Maya R
authors.initials: MR
authors.lastname: Vilà
authors.forename: Ester
authors.initials: E
authors.lastname: López-Gallardo
authors.forename: Abelardo
authors.initials: A
authors.lastname: Solano
authors.forename: Joan C
authors.initials: JC
authors.lastname: Domingo
authors.forename: Josep
authors.initials: J
authors.lastname: Gámez
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pineda
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Capablo
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Antoni L
authors.initials: AL
authors.lastname: Andreu
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.forename: Marta
authors.initials: M
authors.lastname: Giralt
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D006801:Humans; D008067:Lipoma / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012357:RNA, Transfer, Lys / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D012357:RNA, Transfer, Lys