Abstract
BackgroundPeroxisome proliferator-activated receptor (PPAR)γ is a key regulator in adipose tissue. The rare variant Pro12Ala of PPARγ2 is associated with a decreased risk of insulin resistance. Being dietary PPARγ ligands, conjugated linoleic acids (CLAs) received considerable attention because of their effects on body composition, cancer, atherosclerosis, diabetes, obesity and inflammation, although some effects were only demonstrated in animal trials and the results in human studies were not always consistent. In the present study effects of CLA supplementation on genome wide gene expression in adipose tissue biopsies from 11 Ala12Ala and 23 Pro12Pro men were investigated. Subjects underwent four intervention periods (4 wk) in a randomized double blind cross-over design receiving 4.25 g/d of either cis-9, trans-11 CLA, trans-10,cis-12 CLA, 1:1 mixture of both isomers or a reference linoleic acid oil preparation. After each intervention biopsies were taken, whole genome expression microarrays were applied, and genes of interest were verified by realtime PCR.ResultsThe following genes of lipid metabolism were regulated by CLA: LDLR, FASN, SCD, FADS1 and UCP2 were induced, while ABCA1, CD36 and CA3 were repressed. Transcription factors PPARγ, NFAT5, CREB5 and EBF1, the adipokine NAMPT, members of the insulin signaling cascade SORBS1 and IGF1 and IL6ST were repressed, while the adipokine THBS1 and GLUT4 involved in insulin signaling were induced. Compared to trans-10,cis-12 CLA and the CLA mixture the cis-9, trans-11 CLA isomer exerted weaker effects. Only CD36 (-1.2 fold) and THBS1 (1.5 fold) were regulated. The CLA effect on expression of PPARγ and leptin genes depends on the PPARγ2 genotype.ConclusionThe data suggest that the isomer specific influence of CLA on glucose and lipid metabolism is genotype dependent and at least in part mediated by PPARγ.Trial registration: ISRCTN91188075
Highlights
The term conjugated linoleic acids (CLAs) describes a group of 18-carbon fatty acids with 2 conjugated double bonds
Data were based on 34 subjects; one dropped out because he fell ill and three subjects with PPARγ2 Pro12Pro single nucleotide polymorphism (SNP) were excluded because they showed elevated fasting glucose levels according to the WHO criteria during most or all interventions
Few data are available on the effect of individual CLA isomers
Summary
The term CLA describes a group of 18-carbon fatty acids with 2 conjugated double bonds. They are formed as a result of enzymatic hydrogenation of linoleic acid in ruminants and found in lipids of tissue and milk. Being dietary PPARγ ligands, conjugated linoleic acids (CLAs) received considerable attention because of their effects on body composition, cancer, atherosclerosis, diabetes, obesity and inflammation, some effects were only demonstrated in animal trials and the results in human studies were not always consistent. In the present study effects of CLA supplementation on genome wide gene expression in adipose tissue biopsies from 11 Ala12Ala and 23 Pro12Pro men were investigated. After each intervention biopsies were taken, whole genome expression microarrays were applied, and genes of interest were verified by realtime PCR
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