Document Detail


Isomer-specific regulation of differentiating pig preadipocytes by conjugated linoleic acids.
MedLine Citation:
PMID:  16100064     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Conjugated linoleic acids are a group of geometric and positional isomers of linoleic acid that decrease body fat in growing animals by a poorly understood mechanism. The objective of this study was to investigate the isomer-specific effect of CLA on the proliferation and differentiation of pig preadipocytes in primary culture. The effect of CLA on preadipocyte proliferation was determined using cleavage of the tetrazolium salt, WST-1, as a marker for proliferation. Preadipocyte number was decreased in a dose-dependent fashion by trans-12,cis-10 CLA (P < 0.05). No other fatty acid affected preadipocyte number. Differentiation was monitored on d 10 after induction morphologically, enzymatically, and by measuring the mRNA abundance of key adipogenic transcription factors. Both a crude CLA preparation containing a mixture of CLA isomers (CLA-mix) and the pure trans-10,cis-12 CLA isomer inhibited glycerol-3-phosphate dehydrogenase (GPDH) activity in a dose-dependent fashion, with trans-10,cis-12 CLA being more potent (P < 0.01) than the CLA-mix. Cis-9,trans-11 CLA failed to decrease GPDH activity; however, increasing concentrations of cis-9,trans-11 CLA tended to blunt the inhibitory effect of trans-10,cis-12 CLA on GPDH activity (P < 0.09), suggesting that cis-9,trans-11 CLA may antagonize the action of trans-10,cis-12 CLA in porcine adipocytes. Finally, the isomer-specific effect of CLA on adipogenic transcription factor gene expression was investigated. Trans-10,cis-12 CLA decreased expression of peroxisome proliferator-activated receptor gamma (PPAR gamma; P < 0.01) and sterol regulatory element-binding protein-1c (SREBP-1c; P < 0.05) mRNA, while failing to alter the expression of CCAAT/enhancer binding protein alpha (C/EBPalpha) mRNA. Interestingly, both the CLA-mix and the trans-10,cis-12 CLA isomer increased the mRNA abundance of chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF; P < 0.002). No other fatty acid affected COUP-TF mRNA levels. Collectively these data support the concept that CLA decreases fat accretion in pigs, in part by inhibiting preadipocyte proliferation and differentiation, with trans-10,cis-12 CLA being an active isomer eliciting these effects. Furthermore, trans-10,cis-12 CLA inhibits porcine preadipocyte differentiation by a mechanism that involves the down-regulation of PPARgamma and SREBP-1c mRNA. This mechanism is independent of changes in C/EBPalpha mRNA abundance and may involve COUP-TF.
Authors:
T D Brandebourg; C Y Hu
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of animal science     Volume:  83     ISSN:  1525-3163     ISO Abbreviation:  J. Anim. Sci.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-15     Completed Date:  2008-01-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8003002     Medline TA:  J Anim Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2096-105     Citation Subset:  IM    
Affiliation:
Department of Animal Sciences, Oregon State University, Corvallis, 97331, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / cytology,  drug effects*
Animals
CCAAT-Enhancer-Binding Protein-alpha / biosynthesis,  drug effects
COUP Transcription Factor I / biosynthesis,  drug effects
Cell Count / veterinary
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
DNA Primers / chemistry
Dose-Response Relationship, Drug
Fatty Acids / pharmacology
Formazans / analysis
Gene Expression Regulation, Developmental / drug effects*
Glycerolphosphate Dehydrogenase / analysis
Linoleic Acids, Conjugated / pharmacology*
PPAR gamma / biosynthesis,  drug effects
Sterol Regulatory Element Binding Protein 1 / biosynthesis,  drug effects
Swine / physiology*
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-alpha; 0/COUP Transcription Factor I; 0/DNA Primers; 0/Fatty Acids; 0/Formazans; 0/Linoleic Acids, Conjugated; 0/PPAR gamma; 0/Sterol Regulatory Element Binding Protein 1; 0/trans-10,cis-12-conjugated linoleic acid; EC 1.1.-/Glycerolphosphate Dehydrogenase

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