Tissue Distribution and Quantification of the Expression of mRNAs of Peroxisome Proliferator–Activated Receptors and Liver X Receptor-α in Humans: No Alteration in Adipose Tissue of Obese and NIDDM Patients

Abstract

Members of the peroxisome proliferator–activated receptor (PPAR) family might be involved in pathologies with altered lipid metabolism. They participate in the control of the expression of genes involved in lipid metabolism and adipocyte differentiation. In addition, thiazolidinediones improve insulin resistance in vivo by activating PPARγ. However, little is known regarding their tissue distribution and relative expression in humans. Using a quantitative and sensitive reverse transcription (RT)-competitive polymerase chain reaction (PCR) assay, we determined the distribution and relative mRNA expression of the four PPARs (α, β, γ1, and γ2) and liver X receptor-α (LXRα) in the main tissues implicated in lipid metabolism. PPARα and LXRα were mainly expressed in liver, while PPARγ1 predominated in adipose tissue and large intestine. We found that PPARγ2 mRNA was a minor isoform, even in adipose tissue, thus causing question of its role in humans. PPARβ mRNA was present in all the tissues tested at low levels. In addition, PPARγ mRNA was barely detectable in skeletal muscle, suggesting that improvement of insulin resistance with thiazolidinediones may not result from a direct effect of these agents on PPARγ in muscle. Obesity and NIDDM were not associated with change in PPARs and LXRα expression in adipose tissue. The mRNA levels of PPARγ1, the predominant form in adipocytes, did not correlate with BMI, leptin mRNA levels, or fasting insulinemia in 29 subjects with various degrees of obesity. These results indicated that obesity is not associated with alteration in PPAR gene expression in abdominal subcutaneous adipose tissue in humans.