| N-3 polyunsaturated fatty acids suppress insulin-induced SREBP-1c transcription via reduced trans-activating capacity of LXRalpha. | |
| | |
MedLine Citation:
|
PMID: 19716432 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Insulin coordinately up-regulates lipogenic gene transcription via induction of sterol regulatory element binding protein-1c (SREBP-1c). Conversely, polyunsaturated fatty acids (PUFA) decrease lipogenic gene transcription via suppression of SREBP-1c. We therefore examined the ability of n-3 PUFA to mitigate induction of SREBP-1c and its downstream lipogenic targets by insulin in primary rat hepatocyte cultures. Insulin induced expression of SREBP-1c mRNA 5-6 fold as well as rat SREBP-1c promoter activity. These effects were prevented by the n-3 fatty acids eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3, DHA), but not by the monounsaturated fatty acid oleic acid (18:1 n-6, OLA). N-3 fatty acids also effectively prevented insulin induction of the downstream lipogenic enzyme targets fatty acid synthase (FAS) and acetyl carboxyl coenzyme acetyltransferase-1 (ACC-1), and reduced de novo lipogenesis. The SREBP-1c promoter contains an insulin response unit consisting of tandem LXRalpha response elements (LXREs) as well as sites for NF-Y, Sp1, and SREBP-1c itself. The LXREs were identified as a primary site mediating suppression of SREBP-1c transcription by n-3 PUFA. DHA effectively prevented LXRalpha-dependent activation of both the wild type SREBP-1c promoter and the synthetic LXRE-driven promoter, and significantly blunted LXRalpha-dependent activation of a Gal4-LXRalpha chimeric protein thus demonstrating that n-3 PUFA effectively mitigate induction of SREBP-1c by insulin via reduced trans-activation of LXRalpha. |
| | |
Authors:
|
George Howell; Xiong Deng; Chandrahassa Yellaturu; Edwards A Park; Henry G Wilcox; Rajendra Raghow; Marshall B Elam |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2009-08-27 |
Journal Detail:
|
Title: Biochimica et biophysica acta Volume: 1791 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2009 Dec |
Date Detail:
|
Created Date: 2009-11-03 Completed Date: 2010-01-06 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 1190-6 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Binding Sites Fatty Acids, Omega-3 / pharmacology* Insulin / pharmacology* Lipogenesis / genetics Luciferases / metabolism Mutation / genetics Orphan Nuclear Receptors / agonists, antagonists & inhibitors, genetics* Rats Response Elements / genetics Sterol Regulatory Element Binding Protein 1 / genetics* Transcription, Genetic / drug effects* Transcriptional Activation / drug effects* |
| Grant Support | |
ID/Acronym/Agency:
|
1F32DK083210-01/DK/NIDDK NIH HHS; F32 DK083210-01/DK/NIDDK NIH HHS; HL 07641-14/HL/NHLBI NIH HHS; R01 DK059368-07/DK/NIDDK NIH HHS; R01 DK075504-01A1/DK/NIDDK NIH HHS; R01-DK75504-01/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Fatty Acids, Omega-3; 0/Orphan Nuclear Receptors; 0/Sterol Regulatory Element Binding Protein 1; 0/liver X receptor; 11061-68-0/Insulin; EC 1.13.12.-/Luciferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: NMR methods in fragment screening: theory and a comparison with other biophysical techniques.
Next Document: The ngram chief complaint classifier: A novel method of automatically creating chief complaint class...