Nakagawa Hayato, Hayata Yuki, Kawamura Satoshi, Yamada Tomoharu, Fujiwara Naoto, Koike Kazuhiko
Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Cancers (Basel). 2018 Nov 15;10(11):447. doi: 10.3390/cancers10110447.
Metabolic reprogramming for adaptation to the local environment has been recognized as a hallmark of cancer. Although alterations in fatty acid (FA) metabolism in cancer cells have received less attention compared to other metabolic alterations such as glucose or glutamine metabolism, recent studies have uncovered the importance of lipid metabolic reprogramming in carcinogenesis. Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC), and individuals with these conditions exhibit an increased intake of dietary FAs accompanied by enhanced lipolysis of visceral adipose tissue due to insulin resistance, resulting in enormous exogenous FA supplies to hepatocytes via the portal vein and lymph vessels. This "lipid-rich condition" is highly characteristic of obesity- and NASH-driven HCC. Although the way in which HCC cells adapt to such a condition and exploit it to aid their progression is not understood, we recently obtained new insights into this mechanism through lipid metabolic reprogramming. In addition, accumulating evidence supports the importance of lipid metabolic reprogramming in various situations of hepatocarcinogenesis. Thus, in this review, we discuss the latest findings regarding the role of FA metabolism pathways in hepatocarcinogenesis, focusing on obesity- and NASH-driven lipid metabolic reprogramming.
代谢重编程以适应局部环境已被公认为癌症的一个标志。尽管与葡萄糖或谷氨酰胺代谢等其他代谢改变相比，癌细胞中脂肪酸（FA）代谢的改变受到的关注较少，但最近的研究揭示了脂质代谢重编程在致癌过程中的重要性。肥胖和非酒精性脂肪性肝炎（NASH）是肝细胞癌（HCC）众所周知的危险因素，患有这些疾病的个体由于胰岛素抵抗，膳食脂肪酸摄入量增加，同时内脏脂肪组织的脂肪分解增强，导致通过门静脉和淋巴管向肝细胞大量供应外源性脂肪酸。这种“富含脂质的状态”是肥胖和NASH驱动的HCC的高度特征。尽管HCC细胞如何适应这种状态并利用它来促进其进展尚不清楚，但我们最近通过脂质代谢重编程对这一机制有了新的认识。此外，越来越多的证据支持脂质代谢重编程在肝癌发生的各种情况下的重要性。因此，在本综述中，我们讨论了脂肪酸代谢途径在肝癌发生中的作用的最新发现，重点是肥胖和NASH驱动的脂质代谢重编程。
