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Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients.
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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 PPAR gamma. 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 (alpha,beta, gamma1, and gamma2) and liver X receptor-alpha (LXR alpha) in the main tissues implicated in lipid metabolism. PPAR alpha and LXR alpha were mainly expressed in liver, while PPAR gamma1 predominated in adipose tissue and large intestine. We found that PPAR gamma2 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 thiazolidinediones may not result from a direct effect of these agents on PPAR gamma in muscle. Obesity and NIDDM were not associated with change in PPARs and LXR alpha expression in adipose tissue. The mRNA levels of PPAR gamma1, 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.
Adipocytes/chemistry, Adipocytes/cytology, Adipose Tissue/chemistry, Adipose Tissue/metabolism, Base Sequence, Biopsy, Cells, Cultured, Cohort Studies, DNA Primers/chemistry, DNA-Binding Proteins, Diabetes Mellitus, Type 2/genetics, Diabetes Mellitus, Type 2/metabolism, Female, Gene Expression/genetics, Humans, Intestine, Large/chemistry, Intestine, Large/pathology, Intestine, Small/chemistry, Intestine, Small/pathology, Kidney/chemistry, Kidney/pathology, Liver/chemistry, Liver/pathology, Male, Muscle, Skeletal/chemistry, Muscle, Skeletal/metabolism, Nuclear Proteins/genetics, Obesity/genetics, Obesity/metabolism, Orphan Nuclear Receptors, Polymerase Chain Reaction, RNA, Messenger/analysis, RNA, Messenger/genetics, Receptors, Cytoplasmic and Nuclear/genetics, Transcription Factors/genetics
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