Document Detail

Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes.
MedLine Citation:
PMID:  21775116     Owner:  NLM     Status:  MEDLINE    
Conjugated linoleic acid (CLA) reduces adiposity in vivo. However, mechanisms mediating these changes are unclear. Therefore, we treated cultures of human adipocytes with trans-10, cis-12 (10,12) CLA, cis-9, trans-11 (9,11) CLA or other trans fatty acids (FA), and measured indices of lipid metabolism. The lipid-lowering effects of 10,12 CLA were unique, as other trans FA did not reduce TG content to the same extent. Using low levels of [(14)C]-CLA isomers, it was shown that both isomers were readily incorporated into acylglycerols and phospholipids, albeit at lower levels than [(14)C]-oleic or [(14)C]-linoleic acids. When using [(14)C]-acetic acid and [(14)C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within 7-12 h, respectively. The mRNA levels of liver X receptor (LXR)α and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA is due, in part, to the rapid repression of lipogenic transcription factors that regulate MUFA synthesis, suggesting an anti-obesity mechanism unique to this trans FA.
Thomas Obsen; Nils J Faergeman; Soonkyu Chung; Kristina Martinez; Semone Gobern; Olivier Loreau; Martin Wabitsch; Susanne Mandrup; Michael McIntosh
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-19
Journal Detail:
Title:  The Journal of nutritional biochemistry     Volume:  23     ISSN:  1873-4847     ISO Abbreviation:  J. Nutr. Biochem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-15     Completed Date:  2012-09-25     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9010081     Medline TA:  J Nutr Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  580-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
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MeSH Terms
Adipocytes / drug effects*,  metabolism*
Cells, Cultured
Fatty Acids / metabolism
Fatty Acids, Monounsaturated / metabolism
Linoleic Acids, Conjugated / pharmacology*
Lipid Metabolism / drug effects*
Middle Aged
Orphan Nuclear Receptors / genetics,  metabolism
Real-Time Polymerase Chain Reaction
Stearoyl-CoA Desaturase / genetics,  metabolism
Sterol Regulatory Element Binding Protein 1 / genetics,  metabolism
Trans Fatty Acids / metabolism
Transcription Factors / genetics,  metabolism
Triglycerides / biosynthesis
Young Adult
Grant Support
5R01-DK063070/DK/NIDDK NIH HHS; F31DK084812-02/DK/NIDDK NIH HHS; R01 DK063070-08/DK/NIDDK NIH HHS
Reg. No./Substance:
0/Fatty Acids; 0/Fatty Acids, Monounsaturated; 0/Linoleic Acids, Conjugated; 0/Orphan Nuclear Receptors; 0/SREBF1 protein, human; 0/Sterol Regulatory Element Binding Protein 1; 0/Trans Fatty Acids; 0/Transcription Factors; 0/Triglycerides; 0/liver X receptor; EC protein, human; EC Desaturase

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