Document Detail

From sugar to fat: How the transcription factor XBP1 regulates hepatic lipogenesis.
MedLine Citation:
PMID:  19751410     Owner:  NLM     Status:  MEDLINE    
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.
Laurie H Glimcher; Ann-Hwee Lee
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
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:
Created Date:  2009-09-15     Completed Date:  2009-10-23     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E2-9     Citation Subset:  IM    
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MeSH Terms
Carbohydrates / physiology
Cholesterol / deficiency
DNA-Binding Proteins / drug effects,  genetics*,  metabolism
Dietary Carbohydrates / pharmacology*
Dyslipidemias / genetics
Fatty Acids / biosynthesis
Genes, MHC Class II
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
Reg. No./Substance:
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; 97C5T2UQ7J/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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