Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes.
Trans-10,cis-12 conjugated linoleic acid (CLA) has previously been shown to be the CLA isomer responsible for CLA-induced reductions in body fat in animal models, and we have shown that this isomer, but not the cis-9,trans-11 CLA isomer, specifically decreased triglyceride (TG) accumulation in primary human adipocytes in vitro. Here we investigated the mechanism behind the isomer-specific, CLA-mediated reduction in TG accumulation in differentiating human preadipocytes. Trans-10,cis-12 CLA decreased insulin-stimulated glucose uptake and oxidation, and reduced insulin-dependent glucose transporter 4 gene expression. Furthermore, trans-10,cis-12 CLA reduced oleic acid uptake and oxidation when compared with all other treatments. In parallel to CLA's effects on metabolism, trans-10,cis-12 CLA decreased, whereas cis-9,trans-11 CLA increased, the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and several of its downstream target genes when compared with vehicle controls. Transient transfections demonstrated that both CLA isomers antagonized ligand-dependent activation of PPARgamma. Collectively, trans-10,cis-12, but not cis-9, trans-11, CLA decreased glucose and lipid uptake and oxidation and preadipocyte differentiation by altering preadipocyte gene transcription in a manner that appeared to be due, in part, to decreased PPARgamma expression.
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
J Mark
JM
Brown
Maria Sandberg
MS
Boysen
Søren Skov
SS
Jensen
Ron F
RF
Morrison
Jayne
J
Storkson
Renee
R
Lea-Currie
Michael
M
Pariza
Susanne
S
Mandrup
Michael K
MK
McIntosh
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002849:Chromatography, Gas; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D019301:Oleic Acid / Q000493:pharmacokinetics; D009841:Oligonucleotides / Q000737:chemistry; D010100:Oxygen / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D020033:Protein Isoforms; D012313:RNA / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014867:Water / Q000737:chemistry
D000963:Antimetabolites; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D009841:Oligonucleotides; D010743:Phospholipids; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D014867:Water; D002245:Carbon Dioxide; D019301:Oleic Acid; D012313:RNA; D003847:Deoxyglucose; D005947:Glucose; D010100:Oxygen