The purpose of this study was to examine the induction profiles (as judged by quantitative reverse transcription polymerase chain reaction (qRT-PCR)) of peroxisome proliferator-activated receptor (PPAR) α, β, Γ subtypes and major PPAR-target genes bearing a functional peroxisome proliferator responsive element (PPRE) in HepG2 cell model upon feeding with cis-9,trans-11-octadecadienoic acid (9-CLA) or trans-10,cis-12-octadecadienoic acid (10-CLA) or their precursor fatty acids (FAs). HepG2 cells were treated with 100 μmol/L 9-CLA or 10-CLA or their precursor FAs, viz., oleic, linoleic, and trans-11-vaccenic acids against bezafibrate control to evaluate the induction/expression profiles of PPAR α, β, Γ subtypes and major PPAR-target genes bearing a functional PPRE, i.e., fatty acid transporter (FAT), glucose transporter-2 (GLUT-2), liver-type FA binding protein (L-FABP), acyl CoA oxidase-1 (ACOX-1), and peroxisomal bifunctional enzyme (PBE) with reference to β-actin as house keeping gene. Of the three housekeeping genes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH), β-actin, and ubiquitin), β-actin was found to be stable. Dimethyl sulfoxide (DMSO), the common solubilizer of agonists, showed a significantly higher induction of genes analyzed. qRT-PCR profiles of CLAs and their precursor FAs clearly showed upregulation of FAT, GLUT-2, and L-FABP (∼0.5–2.0-fold). Compared to 10-CLA, 9-CLA decreased the induction of the FA metabolizing gene ACOX-1 less than did PBE, while 10-CLA decreased the induction of PBE less than did ACOX-1. Both CLAs and precursor FAs upregulated PPRE-bearing genes, but with comparatively less or marginal activation of PPAR subtypes. This indicates that the binding of CLAs and their precursor FAs to PPAR subtypes results in PPAR activation, thereby induction of the target transporter genes coupled with downstream lipid metabolising genes such as ACOX-1 and PBE. To sum up, the expression profiles of these candidate genes showed that CLAs and their precursor FAs are involved in lipid signalling by modulating the PPAR α, β, or Γ subtype for the indirect activation of the PPAR-target genes, which may in turn be responsible for the supposed health effects of CLA, and that care should be taken while calculating the actual fold induction values of candidate genes with reference to housekeeping gene and DMSO as they may impart false positive results.

Gene-by-diet interactions play an important role in the prevention of several diseases. Conjugated linoleic acids (CLA) are ligands of gene regulators [e.g. peroxisome proliferator-activated receptors (PPAR)] and have anti-inflammatory properties. The aim of the study was to investigate the changes in gene expression in monocytes during the intervention with two trans fatty acids (trans-11 18:1 and trans-12 18:1) and endogenous CLA from trans-11 18:1 as precursor in humans. Monocytes were isolated at baseline and after a 6-week intervention period. The female and male test groups received Sigma 6.0 g trans-11 and trans-12 18:1/day (1 : 1). The control group received control oil. The expression of candidate genes was determined by quantitative RTPCR. Gender- and treatment-related gene expression was found. Due to trans fatty acid intake in both gender subgroups, the relative PPAR gamma expression was up-regulated. In the female test group, the expression of FAT, SCD, COX2 and BCL2 were induced, while in the male test group E-FABP CYP, GLUT4 and PBE were induced. In the male test group compared to controls, a clear increase in gene expression of PPAR gamma and GLUT4 was shown. The results reveal a gender- and treatment-related gene expression. There is no clear indication as to what extent the supplemented trans fatty acids and the synthesized cis-9,trans-11 CLA were involved.