Role of PPAR-α on human liver metabolic dysfunction and carcinogenesis

背景过氧化物酶体激活受体α（PPARα）调节肝脏脂质代谢。然而，目前还不清楚PPARα在肝癌组织中的变化。另一方面，从小鼠的致癌实验来看，过氧化物酶体增殖物诱导的肝癌的发生发展需要过氧化物酶体增殖物激活受体α，过氧化物酶体增殖物激活受体α与肝癌发生发展的关系一直是人们关注的焦点。有没有报告，但是，在人类liver cancer.MethodsThe研究对象是10例接受肝切除术的HCC。我们评估了人肝癌组织和非癌组织中PPARα mRNA的表达，以及PPARα的靶基因肉毒碱棕榈酰转移酶1A（CPT 1A）和细胞周期蛋白D1 mRNA的表达。结果癌组织中PPARα、CPT 1A和G3PDH mRNA的表达量均显著高于非癌组织。Cyclin D1 mRNA在癌组织中的表达水平高于非癌组织。结论肝癌组织和非癌肝组织中PPAR α mRNA和PPARα靶基因mRNA的表达水平表明，肝癌组织中能量的产生主要由脂质而不是碳水化合物，并且通过细胞周期蛋白D抑制细胞凋亡可能与癌症的发展有关。

BackgroundProliferator-activated receptor a (PPARα) regulates lipid metabolism in the liver. It is unclear, however, how PPARα changes in liver cancer tissue. On the other hand, from carcinogenesis experiments using mice, PPARα is necessary for development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer has been the focus of some attention. There have been no reports, however, on findings in human liver cancer.MethodsThe subjects were 10 patients who underwent hepatectomy for HCC. We assessed the expression of PPARα mRNA in human HCC tissue and non-cancerous tissue, as well as the expression of a target gene of PPARα, carnitine palmitoyltransferase 1A (CPT1A) and cyclin D1 mRNA. We also evaluated glyceraldehyde 3-phosphate dehydrogenase (G3PDH), a key enzyme in the glycolytic system.ResultsThe amounts of PPARα, CPT1A and G3PDH mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of Cyclin D1 mRNA tend to be higher in cancerous sections than in non-cancerous sections. There was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections.ConclusionThe present investigation of the levels of PPARα mRNA and mRNAs for PPARα target gene in human HCC and non-cancerous liver tissue suggest that lipids rather than carbohydrates may be mainly used for energy production in HCC, and that the inhibition of apoptosis via cyclin D may be linked to the development of cancer.