| From sugar to fat: How the transcription factor XBP1 regulates hepatic lipogenesis. | |
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MedLine Citation:
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PMID: 19751410 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipogenesis occurs primarily in the liver, where dietary carbohydrates control the expression of key enzymes in glycolytic and lipogenic pathways. We have recently discovered that the transcription factor XBP1, best known as a key regulator of the unfolded protein response (UPR), is required for de novo fatty acid synthesis in the liver, a function unrelated to its role in the UPR.(1) XBP1 protein expression is induced in the liver by a high carbohydrate diet and directly controls the induction of critical genes involved in fatty acid synthesis. Specific deletion of XBP1 in adult liver using an inducible approach results in profound hypocholesterolemia and hypotriglyceridemia, which could be attributed to diminished production of lipids in the liver. Notably, this phenotype is not associated with fatty liver (hepatic steatosis) or significant compromise in protein secretion. XBP1 joins an already rich field of transcriptional regulatory proteins in the control of hepatic lipogenesis. Its function in lipogenesis appears to be highly significant as evidenced by the phenotype of the genetic mutant strain. A more complete understanding of the mechanisms by which XBP1 accelerates de novo fatty acid synthesis in the liver while preserving normal hepatic lipid composition is highly relevant to the treatment of diseases such as atherosclerosis and metabolic syndrome that are associated with dyslipidemia. Since excess fat accumulation in the liver could result from increased hepatic fatty acid synthesis, compounds that inhibit XBP1 activation may also be useful therapeutics for the treatment of human alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), increasingly common causes of morbidity and mortality in the United States. |
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Authors:
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Laurie H Glimcher; Ann-Hwee Lee |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Annals of the New York Academy of Sciences Volume: 1173 Suppl 1 ISSN: 1749-6632 ISO Abbreviation: Ann. N. Y. Acad. Sci. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-15 Completed Date: 2009-10-23 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 7506858 Medline TA: Ann N Y Acad Sci Country: United States |
Other Details:
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Languages: eng Pagination: E2-9 Citation Subset: IM |
Affiliation:
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Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA. lglimche@hsph.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Carbohydrates / physiology Cholesterol / deficiency DNA-Binding Proteins / drug effects, genetics*, metabolism Dietary Carbohydrates / pharmacology* Dyslipidemias / genetics Fatty Acids / biosynthesis Genes, MHC Class II Humans Insulin Resistance / genetics Lipids / biosynthesis* Liver / physiology* Metabolic Diseases / genetics* Metabolic Syndrome X / epidemiology Obesity / epidemiology RNA, Messenger / genetics Transcription Factors / drug effects, genetics*, metabolism Triglycerides / deficiency |
| Grant Support | |
ID/Acronym/Agency:
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AI32412/AI/NIAID NIH HHS; P01 AI056296-05/AI/NIAID NIH HHS; P01 AI56296/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carbohydrates; 0/DNA-Binding Proteins; 0/Dietary Carbohydrates; 0/Fatty Acids; 0/Lipids; 0/RNA, Messenger; 0/Transcription Factors; 0/Triglycerides; 0/regulatory factor X transcription factors; 57-88-5/Cholesterol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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