Isomer-specific regulation of metabolism and PPARγ 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; Michael K. McIntosh

Journal of Lipid Research (Jul 2003)

Isomer-specific regulation of metabolism and PPARγ 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,
Michael K. McIntosh

Affiliations

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

Journal volume & issue: Vol. 44, no. 7
pp. 1287 – 1300

Abstract

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

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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