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
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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DOI：
10.2337/diabetes.46.8.1319
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发表时间：
1997-08-01
期刊：
影响因子：
7.7
通讯作者：
Vidal, H
中科院分区：
文献类型：
--
作者：
Auboeuf, D;Rieusset, J;Vidal, H
过氧化物酶体增殖物激活受体 (PPAR) 家族的成员可能与脂质代谢改变的病理有关。它们参与脂质代谢和脂肪细胞分化相关基因表达的控制。此外，噻唑烷二酮类通过激活 PPAR γ 改善体内胰岛素抵抗。然而，人们对它们的组织分布和在人类中的相对表达知之甚少。使用定量和灵敏的逆转录 (RT) 竞争性聚合酶链反应 (PCR) 测定，我们确定了四种 PPAR（α、β、γ 1 和 γ 2）和肝脏 X 受体-α (LXR α) 在参与脂质代谢的主要组织中的分布和相对 mRNA 表达。 PPARα和LXRα主要在肝脏中表达，而PPARγ1主要在脂肪组织和大肠中表达。我们发现 PPAR gamma 2 mRNA 是一种次要亚型，即使在脂肪组织中也是如此，因此引发了对其在人类中的作用的质疑。所有测试的组织中 PPAR β mRNA 均呈低水平存在。此外，骨骼肌中几乎检测不到 PPAR γ mRNA，这表明噻唑烷二酮类药物改善胰岛素抵抗可能不会导致这些药物对肌肉中 PPAR γ 产生直接影响。肥胖和 NIDDM 与脂肪组织中 PPAR 和 LXR α 表达的变化无关。在 29 名不同程度肥胖的受试者中，PPAR γ 1（脂肪细胞中的主要形式）的 mRNA 水平与 BMI、瘦素 mRNA 水平或空腹胰岛素血症无关。这些结果表明，肥胖与人类腹部皮下脂肪组织中 PPAR 基因表达的改变无关。
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, thiazolidine-diones 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, gamma 1, and gamma 2) 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 gamma 1 predominated 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 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 gamma 1, 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.