Isomer-specific effects of CLA on gene expression in human adipose tissue depending on PPARgamma2 P12A polymorphism: a double blind, randomized, controlled cross-over study.
BACKGROUND
Peroxisome proliferator-activated receptor (PPAR)gamma is a key regulator in adipose tissue. The rare variant Pro12Ala of PPARgamma2 is associated with a decreased risk of insulin resistance. Being dietary PPARgamma 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.


RESULTS
The 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 PPARgamma, 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 PPARgamma and leptin genes depends on the PPARgamma2 genotype.


CONCLUSIONS
The data suggest that the isomer specific influence of CLA on glucose and lipid metabolism is genotype dependent and at least in part mediated by PPARgamma.


BACKGROUND
http://www.controlled-trials.com: ISRCTN91188075.
Herrmann
J
J
Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe and Kiel, Germany. julia.herrmann@mri.bund.de
Rubin
D
D
Häsler
R
R
Helwig
U
U
Pfeuffer
M
M
Auinger
A
A
Laue
C
C
Winkler
P
P
Schreiber
S
S
Bell
D
D
Schrezenmeir
J
J
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000368:Aged; D000090943:Delta-5 Fatty Acid Desaturase; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000090943:Delta-5 Fatty Acid Desaturase; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; C000716847:FADS1 protein, human
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