The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia
Summary: 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 ∼60% reduction in liver zinc-finger protein-125 (Zfp125) expression. Zfp125 is a Foxo1-inducible tr...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717318776 |
| _version_ | 1811324018630852608 |
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| author | Gustavo W. Fernandes Barbara M.L.C. Bocco Tatiana L. Fonseca Elizabeth A. McAninch Sungro Jo Lattoya J. Lartey InSug O-Sullivan Terry G. Unterman Nailliw Z. Preite Robin M. Voigt Christopher B. Forsyth Ali Keshavarzian Richárd Sinkó Allison B. Goldfine Mary E. Patti Miriam O. Ribeiro Balázs Gereben Antonio C. Bianco |
| author_facet | Gustavo W. Fernandes Barbara M.L.C. Bocco Tatiana L. Fonseca Elizabeth A. McAninch Sungro Jo Lattoya J. Lartey InSug O-Sullivan Terry G. Unterman Nailliw Z. Preite Robin M. Voigt Christopher B. Forsyth Ali Keshavarzian Richárd Sinkó Allison B. Goldfine Mary E. Patti Miriam O. Ribeiro Balázs Gereben Antonio C. Bianco |
| author_sort | Gustavo W. Fernandes |
| collection | DOAJ |
| description | Summary: 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 ∼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. Keywords: deiodinase, steatosis, cholesterol, triglycerides, zinc finger protein 125, liver, hepatocytes, transcriptional repressor |
| first_indexed | 2024-04-13T14:06:50Z |
| format | Article |
| id | doaj.art-a4785ccf0adc442d8ad47261ca8b28e7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T14:06:50Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a4785ccf0adc442d8ad47261ca8b28e72022-12-22T02:43:54ZengElsevierCell Reports2211-12472018-01-01222523534The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and HypercholesterolemiaGustavo W. Fernandes0Barbara M.L.C. Bocco1Tatiana L. Fonseca2Elizabeth A. McAninch3Sungro Jo4Lattoya J. Lartey5InSug O-Sullivan6Terry G. Unterman7Nailliw Z. Preite8Robin M. Voigt9Christopher B. Forsyth10Ali Keshavarzian11Richárd Sinkó12Allison B. Goldfine13Mary E. Patti14Miriam O. Ribeiro15Balázs Gereben16Antonio C. Bianco17Division of Endocrinology and Metabolism, Rush University Medical Center, Chicago, IL; Program in Translational Medicine, Federal University of Sao Paulo, Sao Paulo, BrazilDivision of Endocrinology and Metabolism, Rush University Medical Center, Chicago, IL; Program in Translational Medicine, Federal University of Sao Paulo, Sao Paulo, BrazilDivision of Endocrinology and Metabolism, Rush University Medical Center, Chicago, ILDivision of Endocrinology and Metabolism, Rush University Medical Center, Chicago, ILDivision of Endocrinology and Metabolism, Rush University Medical Center, Chicago, ILDivision of Endocrinology and Metabolism, Rush University Medical Center, Chicago, ILSection of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, ILSection of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, ILDivision of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, ILDivision of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, ILDivision of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, ILDivision of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, ILDepartment of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, HungaryJoslin Diabetes Center, Harvard Medical School, Boston, MAJoslin Diabetes Center, Harvard Medical School, Boston, MADevelopmental Disorders Program, Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo, BrazilDepartment of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, HungaryDivision of Endocrinology and Metabolism, Rush University Medical Center, Chicago, IL; Corresponding authorSummary: 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 ∼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. Keywords: deiodinase, steatosis, cholesterol, triglycerides, zinc finger protein 125, liver, hepatocytes, transcriptional repressorhttp://www.sciencedirect.com/science/article/pii/S2211124717318776 |
| spellingShingle | Gustavo W. Fernandes Barbara M.L.C. Bocco Tatiana L. Fonseca Elizabeth A. McAninch Sungro Jo Lattoya J. Lartey InSug O-Sullivan Terry G. Unterman Nailliw Z. Preite Robin M. Voigt Christopher B. Forsyth Ali Keshavarzian Richárd Sinkó Allison B. Goldfine Mary E. Patti Miriam O. Ribeiro Balázs Gereben Antonio C. Bianco The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia Cell Reports |
| title | The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia |
| title_full | The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia |
| title_fullStr | The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia |
| title_full_unstemmed | The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia |
| title_short | The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia |
| title_sort | foxo1 inducible transcriptional repressor zfp125 causes hepatic steatosis and hypercholesterolemia |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717318776 |
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