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

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dc.contributor.authorFernandes G.W.
dc.contributor.authorBocco B.M.L.C.
dc.contributor.authorFonseca T.L.
dc.contributor.authorMcAninch E.A.
dc.contributor.authorJo S.
dc.contributor.authorLartey L.J.
dc.contributor.authorO-Sullivan I.
dc.contributor.authorUnterman T.G.
dc.contributor.authorPreite N.Z.
dc.contributor.authorVoigt R.M.
dc.contributor.authorForsyth C.B.
dc.contributor.authorKeshavarzian A.
dc.contributor.authorSinko R.
dc.contributor.authorGoldfine A.B.
dc.contributor.authorPatti M.E.
dc.contributor.authorRibeiro M.O.
dc.contributor.authorGereben B.
dc.contributor.authorBianco A.C.
dc.date.accessioned2024-03-12T23:59:54Z
dc.date.available2024-03-12T23:59:54Z
dc.date.issued2018
dc.description.abstract© 2017 The AuthorsLiver-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 ∼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. Mice with liver-specific disruption of the type 2 deiodinase gene are resistant to both diet-induced obesity and hepatosteatosis. Fernandes et al. show that this is due to a reduction in liver expression of zinc-finger protein-125, a Foxo1-inducible transcriptional repressor that causes lipid accumulation by reducing hepatic secretion of VLDL.
dc.description.firstpage523
dc.description.issuenumber2
dc.description.lastpage534
dc.description.volume22
dc.identifier.doi10.1016/j.celrep.2017.12.053
dc.identifier.issn2211-1247
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/35645
dc.relation.ispartofCell Reports
dc.rightsAcesso Aberto
dc.subject.otherlanguagecholesterol
dc.subject.otherlanguagedeiodinase
dc.subject.otherlanguagehepatocytes
dc.subject.otherlanguageliver
dc.subject.otherlanguagesteatosis
dc.subject.otherlanguagetranscriptional repressor
dc.subject.otherlanguagetriglycerides
dc.subject.otherlanguagezinc finger protein 125
dc.titleThe Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia
dc.typeArtigo
local.scopus.citations18
local.scopus.eid2-s2.0-85041213349
local.scopus.subjectAnimals
local.scopus.subjectDNA-Binding Proteins
local.scopus.subjectFatty Liver
local.scopus.subjectForkhead Box Protein O1
local.scopus.subjectHypercholesterolemia
local.scopus.subjectMice
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85041213349&origin=inward
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