Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARγ activity in primary cultures of human adipocytes

Arion Kennedy, Soonkyu Chung, Kathleen LaPoint, Oluwatoyin Fabiyi, Michael K. McIntosh

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

We previously demonstrated that trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) causes human adipocyte delipidation, insulin resistance, and inflammation in part by attenuating PPARγ target gene expression. We hypothesized that CLA antagonizes the activity of PPARγ in an isomer-specific manner. 10,12 CLA, but not cis-9, trans-11 (9,11) CLA, suppressed ligand-stimulated activation of a peroxisome proliferator response element-luciferase reporter. This decreased activation of PPARγ by 10,12 CLA was accompanied by an increase in PPARγ and extracellular signal-related kinase (ERK)1/2 phosphorylation, followed by decreased PPARγ protein levels. To investigate if 10,12 CLA-mediated delipidation was preventable with a PPARγ ligand (BRL), cultures were treated for 1 wk with 10,12 CLA or 10,12 CLA + BRL and adipogenic gene and protein expression, glucose uptake, and triglyceride (TG) were measured. BRL cosupplementation completely prevented 10,12 CLA suppression of adipocyte fatty acid-binding protein, lipoprotein lipase, and perilipin mRNA levels without preventing reductions in PPARγ or insulin-dependent glucose transporter 4 (GLUT4) expression, glucose uptake, or TG. Lastly, we investigated the impact of CLA withdrawal in the absence or presence of BRL for 2 wk. CLA withdrawal did not rescue CLA-mediated reductions in adipogenic gene and protein expression. In contrast, BRL supplementation for 2 wk following CLA withdrawal rescued mRNA levels of PPARγ target genes. However, the levels of PPARγ and GLUT4 protein and TG were only partially rescued by BRL. Collectively,wedemonstrate for the first time, to our knowledge, that 10,12 CLA antagonizes ligand-dependent PPARγ activity, possibly via PPARγ phosphorylation by ERK.

Original languageEnglish (US)
Pages (from-to)455-461
Number of pages7
JournalJournal of Nutrition
Volume138
Issue number3
StatePublished - Mar 1 2008

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Conjugated Linoleic Acids
Peroxisome Proliferator-Activated Receptors
conjugated linoleic acid
adipocytes
Adipocytes
Ligands
Triglycerides
Facilitative Glucose Transport Proteins
glucose transporters
triacylglycerols
Gene Expression
trans-10,cis-12-conjugated linoleic acid
ligands
gene expression
Proteins
Phosphotransferases
phosphorylation
phosphotransferases (kinases)
Phosphorylation
protein synthesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARγ activity in primary cultures of human adipocytes. / Kennedy, Arion; Chung, Soonkyu; LaPoint, Kathleen; Fabiyi, Oluwatoyin; McIntosh, Michael K.

In: Journal of Nutrition, Vol. 138, No. 3, 01.03.2008, p. 455-461.

Research output: Contribution to journalArticle

Kennedy, Arion ; Chung, Soonkyu ; LaPoint, Kathleen ; Fabiyi, Oluwatoyin ; McIntosh, Michael K. / Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARγ activity in primary cultures of human adipocytes. In: Journal of Nutrition. 2008 ; Vol. 138, No. 3. pp. 455-461.
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