The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia

Autor(es):Mostrar menos -

Fernandes, Gustavo W. ^{[1, 2]} ; Bocco, Barbara M. L. C. ^{[1, 2]} ; Fonseca, Tatiana L. ^[1] ; McAninch, Elizabeth A. ^[1] ; Jo, Sungro ^[1] ; Lartey, Lattoya J. ^[1] ; O-Sullivan, InSug ^[3] ; Unterman, Terry G. ^[3] ; Preite, Nailliw Z. ^[4] ; Voigt, Robin M. ^[4] ; Forsyth, Christopher B. ^[4] ; Keshavarzian, Ali ^[4] ; Sinko, Richard ^[5] ; Goldfine, Allison B. ^[6] ; Patti, Mary E. ^[6] ; Ribeiro, Miriam O. ^[7] ; Gereben, Balazs ^[5] ; Bianco, Antonio C. ^[1]

Afiliação do(s) autor(es)

^[1] Rush Univ, Med Ctr, Div Endocrinol & Metab, Chicago, IL 60612 - USA

^[2] Univ Fed Sao Paulo, Program Translat Med, Sao Paulo - Brazil

^[3] Univ Illinois, Coll Med, Dept Med, Sect Endocrinol Diabet & Metab, Chicago, IL - USA

^[4] Rush Univ, Div Digest Dis & Nutr, Med Ctr, Chicago, IL 60612 - USA

^[5] Hungarian Acad Sci, Inst Expt Med, Dept Endocrine Neurobiol, Budapest - Hungary

^[6] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA - USA

^[7] Univ Prebiteriana Mackenzie, Ctr Biol Sci & Hlth, Dev Disorders Program, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 22, n. 2, p. 523-534, JAN 9 2018.
• Citações Web of Science: 7

Resumo

Liver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in resistance to both diet-induced obesity and liver steatosis in mice. Here, we report that this is explained by an similar to 60% reduction in liver zinc-finger protein-125 (Zfp125) expression. Zfp125 is a Foxo1-inducible transcriptional repressor that causes lipid accumulation in the AML12 mouse hepatic cell line and liver steatosis in mice by reducing liver secretion of triglycerides and hepatocyte efflux of cholesterol. Zfp125 acts by repressing 18 genes involved in lipoprotein structure, lipid binding, and transport. The ApoE promoter contains a functional Zfp125-binding element that is also present in 17 other lipid-related genes repressed by Zfp125. While liver-specific knockdown of Zfp125 causes an ``Alb-D2KO-like'' metabolic phenotype, liver-specific normalization of Zfp125 expression in Alb-D2KO mice rescues the phenotype, restoring normal susceptibility to diet-induced obesity, liver steatosis, and hypercholesterolemia. (AU)

• Processo FAPESP: 11/21847-6 - Papel do receptor adrenérgico beta1 no desenvolvimento da doença hepática não-alcoólica
• Beneficiário: Miriam Oliveira Ribeiro
• Linha de fomento: Auxílio à Pesquisa - Regular