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Journal of Lipid Research, Vol. 44, 1287-1300, July 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Isomer-specific regulation of metabolism and PPAR signaling by CLA in human preadipocytes

J. Mark Brown^*, Maria Sandberg Boysen, Søren Skov Jensen, Ron F. Morrison^*, Jayne Storkson, Renee Lea-Currie^**, Michael Pariza, Susanne Mandrup and Michael K. McIntosh^1,*

^* Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
Department of Food Microbiology and Toxicology, Food Research Institute, University of Wisconsin-Madison, Madison, WI 53706
^** Zen Bio, Inc., 3200 Chapel Hill-Nelson Boulevard, Suite 104, Research Triangle Park, NC 27709

¹ To whom correspondence should be addressed. e-mail: mkmcinto{at}uncg.edu

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 adiopcytes 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 (PPAR) and several of its downstream target genes when compared with vehicle controls. Transient transfections demonstrated that both CLA isomers antagonized ligand-dependent activation of PPAR.

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 PPAR expression.

Abbreviations: ACBP, acyl-CoA binding protein; ACC, acetyl-CoA carboxylase; aP2/FABP, adipocyte fatty acid binding protein; BCA, bicinchoninic acid; BMI, body mass index; BSA, bovine serum albumin; CD-36, fatty acid translocase; C/EBP, CAAT/enhancer binding protein ; CLA, conjugated linoleic acid; GC, gas chromatography; GLUT4, insulin-dependent glucose transporter 4; GPDH, glycerol-3-phosphate dehydrogenase; HSL, hormone-sensitive lipase; IBMX, isobutylmethylxanthine; LA, linoleic acid; LPL, lipoprotein lipase; MUFA, monounsaturated fatty acid; ORO, oil red O; PPAR, peroxisome proliferator-activated receptor; PPRE, peroxisome proliferator response element; SCD-1, stearoyl-CoA desaturase-1; SFA, saturated fatty acid; SV, stromal vascular; TG, triglyceride

Supplementary key words conjugated linoleic acid • fatty acids • lipid metabolism • glucose metabolism • triglycerides • peroxisome proliferator-activated receptor gamma

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