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 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.

Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus

“…FENO did not significantly reduce fasting plasma NEFA or glucose concentrations and did not alter adipocyte sensitivity to insulin, yet it reduced the plasma triacylglycerol concentration by a similar amount to that observed with PIO. These findings indicate that FENO exerts a direct inhibitory effect on hepatic VLDL synthesis/secretion or enhances triacylglycerol clearance from the circulation [38,39]. Fibrates, which possess modest PPAR-α activity, stimulate intravascular lipoprotein lipolysis, enhancing lipoprotein lipase (LPL) activity and reducing the expression of apoCIII, a natural LPL inhibitor.…”

Importance of blood cellular genomic profile in coronary heart disease

“…Reagents were obtained from RevertAid TM first strand cDNA synthesis kit (Fermentas). cDNA of each sample was amplified by PCR using specific primers for genes coding for PPARs (a, c), LXRa, CD36, LDLR and b 2 microglobulin (b 2 M) [19][20][21]. b 2 M amplification was used as a control for RNA loading and efficiency of reverse transcription.…”

“…Cells were seeded at 2Â10 5 cells/well in 24-well culture plates and subsequently exposed to growth medium without or with mevastatin (30lM) for 24 h at 37°C in 5% CO 2 atmosphere. At the end of the incubation period, these cells together with mononuclear cells (obtained from CHD patients receiving 20 mg of atorvastatin orally daily) were processed for RNA isolation [18] followed by RT-PCR using specific primers for genes coding for PPAR (a, c), LXRa and B 2 M [19][20][21]. These culture experiments were done in triplicate to check the reproducibility of the data.…”

Peroxisome proliferator-activated receptor γ ligand-induced growth inhibition of human hepatocellular carcinoma

“…Such results suggest that ligands of PPARγ may serve as a biological modifier in human cancers and the therapeutic potential should be further investigated. Human liver tissue has been reported to express PPARγ (Auboeuf et al, 1997;Vidal-Puig et al, 1997), however, expression of PPARγ in human hepatocellular carcinoma (HCC) and the effect of PPARγ agonists have not yet been studied and this study was designed to investigate that.…”