TISSUE DISTRIBUTION AND QUANTIFICATION OF THE EXPRESSION OF MESSENGER-RNAS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS AND LIVER-X-RECEPTOR-ALPHA IN HUMANS - NO ALTERATION IN ADIPOSE-TISSUE OF OBESE AND NIDDM PATIENTS

Members of the peroxisome proliferator-activated receptor (PPAR) famil y might be involved in pathologies with altered lipid metabolism. They participate in the control of the expression of genes involved in lip id metabolism and adipocyte differentiation. In addition, thiazolidine -diones improve insulin resistance in vivo by activating PPAR gamma. H owever, little is known regarding their tissue distribution and relati ve expression in humans. Using a quantitative and sensitive reverse tr anscription (RT)-competitive polymerase chain reaction (PCR) assay, we determined the distribution and relative mRNA expression of the four PPARs (alpha, beta, gamma 1, and gamma 2) and liver X receptor-alpha ( LXR alpha) in the main tissues implicated in lipid metabolism. PPAR al pha and LXR alpha were mainly expressed in liver, while PPAR gamma 1 p redominated in adipose tissue and large intestine. We found that PPAR gamma 2 mRNA was a minor isoform, even in adipose tissue, thus causing question of its role in humans. PPAR beta mRNA was present in all the tissues tested at low levels. In addition, PPAR gamma mRNA was barely detectable in skeletal muscle, suggesting that improvement of insulin resistance with thiazolidine-diones may not result hom a direct effec t of these agents on PPAR gamma in muscle. Obesity and NIDDM were not associated with change in PPARs and LXR alpha expression in adipose ti ssue. The mRNA levels of PPAR gamma 1, the predominant form in adipocy tes, did not correlate with BMI, leptin mRNA levels, or fasting insuli nemia in 29 subjects with various degrees of obesity. These results in dicated that obesity is not associated with alteration in PPAR gene ex pression in abdominal subcutaneous adipose tissue in humans.