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

增殖物激活受体a(PPARα)调节肝脏的脂类代谢。然而，目前还不清楚PPARα在肝癌组织中的变化情况。另一方面，从小鼠的致癌实验来看，PPARα在过氧化物酶体增殖物诱导的肝癌的发生发展过程中是必需的，PPARα与肝癌发生的关系一直是人们关注的焦点。然而，目前还没有关于人类肝癌的研究结果的报道。我们检测了PPARα在人肝细胞癌组织和癌旁组织中的表达，以及PPARα靶基因肉碱棕榈酰基转移酶1A和细胞周期蛋白D1mRNA的表达。结果PPARα、CPT1a和G3PDH在癌组织中的表达明显高于非癌组织。癌组织中Cyclin D1mRNA的表达水平明显高于非癌组织。结论PPARαα和PPARα靶基因mRNAs在人肝细胞癌和非癌肝组织中的表达水平表明，肝细胞癌的能量产生可能主要来自脂类而不是碳水化合物，通过细胞周期蛋白D抑制细胞凋亡可能与肿瘤的发生有关。

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.