脂代谢与原发性肝癌相关性研究进展
Research Progress on the Correlation between Lipid Metabolism and Primary Liver Cancer
摘要: 脂代谢是机体重要代谢之一,肝脏作为脂质合成、储存以及代谢的中心器官,二者相互影响。肿瘤细胞所处的局部环境称为肿瘤微环境,为适应肿瘤微环境而发生的代谢改变称为代谢重编。目前脂代谢与肝癌之间的相关性尚不完全清楚,肝癌脂代谢重编的具体过程亦尚未完全揭示。本文介绍了肝癌发生、发展各阶段脂代谢特点,总结了肝癌脂代谢重编过程的最新发现,旨在探究脂代谢在肝癌发生、发展以及预后中的作用,为肝癌防治提供新的思路与依据。
Abstract: Lipid metabolism is one of the important metabolic processes in the body, and the liver is the central organ for lipid synthesis, storage, and metabolism, with a mutual influence between them. The local environment in which the tumour cells are located is called the tumor microenvironment, and the metabolic changes that occur to adapt to the tumor microenvironment are called metabolic reprogramming. At present, the relationship between lipid metabolism and liver cancer is not completely clear, and the specific process of lipid metabolic reprogramming in liver cancer has not yet been fully elucidated. This review introduces the lipid metabolic characteristics of liver cancer at each stage of its occurrence and development, summarizes the latest findings on the lipid metabolic reprogramming process in liver cancer, and aims to explore the role of lipid metabolism in the occurrence, development, and prognosis of liver cancer, providing new ideas and evidence for the prevention and treatment of liver cancer.
文章引用:邹可, 黄英. 脂代谢与原发性肝癌相关性研究进展[J]. 临床医学进展, 2025, 15(1): 1084-1091. https://doi.org/10.12677/acm.2025.151145

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] Feng, R., Su, Q., Huang, X., Basnet, T., Xu, X. and Ye, W. (2022) Cancer Situation in China: What Does the China Cancer Map Indicate from the First National Death Survey to the Latest Cancer Registration? Cancer Communications, 43, 75-86. [Google Scholar] [CrossRef] [PubMed]
[3] Jinjuvadia, R., Patel, S. and Liangpunsakul, S. (2014) The Association between Metabolic Syndrome and Hepatocellular Carcinoma. Journal of Clinical Gastroenterology, 48, 172-177. [Google Scholar] [CrossRef] [PubMed]
[4] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版) [J]. 中华糖尿病杂志, 2018, 10(1): 4-67.
[5] Chavez-Tapia, N.C., Murúa-Beltrán Gall, S., Ordoñez-Vázquez, A.L., Nuño-Lambarri, N., Vidal-Cevallos, P. and Uribe, M. (2022) Understanding the Role of Metabolic Syndrome as a Risk Factor for Hepatocellular Carcinoma. Journal of Hepatocellular Carcinoma, 9, 583-593. [Google Scholar] [CrossRef] [PubMed]
[6] 陈小彬, 高帅, 梅学鹏, 等. 代谢综合征与肝细胞癌的关系及机制研究进展[J]. 中国普外基础与临床杂志, 2021, 28(7): 969-973.
[7] Brault, C. and Schulze, A. (2016) The Role of Glucose and Lipid Metabolism in Growth and Survival of Cancer Cells. In: Cramer, T. and Schmitt, C.A., Eds., Recent Results in Cancer Research, Springer International Publishing, 1-22. [Google Scholar] [CrossRef] [PubMed]
[8] 冯洁, 潘勤聪. 血清总胆汁酸及血脂对慢性乙型肝炎肝纤维化的诊断效能[J]. 中西医结合肝病杂志, 2021, 31(10): 930-932.
[9] Wu, T., Zheng, X., Yang, M., Zhao, A., Li, M., Chen, T., et al. (2017) Serum Lipid Alterations Identified in Chronic Hepatitis B, Hepatitis B Virus-Associated Cirrhosis and Carcinoma Patients. Scientific Reports, 7, Article No. 42710. [Google Scholar] [CrossRef] [PubMed]
[10] Sitia, G., Aiolfi, R., Di Lucia, P., Mainetti, M., Fiocchi, A., Mingozzi, F., et al. (2012) Antiplatelet Therapy Prevents Hepatocellular Carcinoma and Improves Survival in a Mouse Model of Chronic Hepatitis B. Proceedings of the National Academy of Sciences, 109, 2165-2172. [Google Scholar] [CrossRef] [PubMed]
[11] Su, I.J., Hsieh, W.C., Tsai, H.W., et al. (2013) Chemoprevention and Novel Therapy for Hepatocellular Carcinoma Associated with Chronic Hepatitis B Virus Infection. Hepatobiliary Surgery and Nutrition, 2, 37-39.
[12] Cho, H.K., Kim, S.Y., Yoo, S.K., Choi, Y.H. and Cheong, J. (2014) Fatty Acids Increase Hepatitis B Virus X Protein Stabilization and HBX‐Induced Inflammatory Gene Expression. The FEBS Journal, 281, 2228-2239. [Google Scholar] [CrossRef] [PubMed]
[13] Teng, C., Hsieh, W., Yang, C., Su, H., Tsai, T., Sung, W., et al. (2015) A Biphasic Response Pattern of Lipid Metabolomics in the Stage Progression of Hepatitis B Virus X Tumorigenesis. Molecular Carcinogenesis, 55, 105-114. [Google Scholar] [CrossRef] [PubMed]
[14] Wu, Y., Peng, X., Zhu, Y., Yan, X., Chen, W. and Lin, X. (2016) Hepatitis B Virus X Protein Induces Hepatic Steatosis by Enhancing the Expression of Liver Fatty Acid Binding Protein. Journal of Virology, 90, 1729-1740. [Google Scholar] [CrossRef] [PubMed]
[15] Braun, D., Abia, W.A., Šarkanj, B., Sulyok, M., Waldhoer, T., Erber, A.C., et al. (2022) Mycotoxin-Mixture Assessment in Mother-Infant Pairs in Nigeria: From Mothers’ Meal to Infants’ Urine. Chemosphere, 287, Article ID: 132226. [Google Scholar] [CrossRef] [PubMed]
[16] Wang, T., Li, X., Liao, G., Wang, Z., Han, X., Gu, J., et al. (2024) AFB1 Triggers Lipid Metabolism Disorders through the PI3K/AKT Pathway and Mediates Apoptosis Leading to Hepatotoxicity. Foods, 13, Article No. 163. [Google Scholar] [CrossRef] [PubMed]
[17] Eraslan, G., Sarıca, Z.S., Bayram, L.Ç., Tekeli, M.Y., Kanbur, M. and Karabacak, M. (2017) The Effects of Diosmin on Aflatoxin-Induced Liver and Kidney Damage. Environmental Science and Pollution Research, 24, 27931-27941. [Google Scholar] [CrossRef] [PubMed]
[18] Tan, S., Qiu, X., Yu, H., Zeng, X., Xiao, Z., Li, L., et al. (2009) Synergistic Action of Clonorchiasis, HBV Infection and Alcohol Consumption on Primary Hepatocellular Carcinoma. Clinical Oncology and Cancer Research, 6, 104-112. [Google Scholar] [CrossRef
[19] Marié, C., Fouquet, G., Courtois, A., Amrathlal, R.S., Jankovsky, N., Ouled-Haddou, H., et al. (2022) Mechanisms of Chronic Alcohol Exposure-Induced Aggressiveness in Cellular Model of HCC and Recovery after Alcohol Withdrawal. Cellular and Molecular Life Sciences, 79, Article No. 366. [Google Scholar] [CrossRef] [PubMed]
[20] French, S.W. (2016) Chronic Alcohol Binging Injures the Liver and Other Organs by Reducing NAD+ Levels Required for Sirtuin’s Deacetylase Activity. Experimental and Molecular Pathology, 100, 303-306. [Google Scholar] [CrossRef] [PubMed]
[21] You, M., Jogasuria, A., Taylor, C., et al. (2015) Sirtuin 1 Signaling and Alcoholic Fatty Liver Disease. HepatoBiliary Surgery and Nutrition, 4, 88-100.
[22] Ma, G., Liu, Y., Zhang, Q., Zhang, B., Zhao, N., Wang, Q., et al. (2014) Pre-Endurance Training Prevents Acute Alcoholic Liver Injury in Rats through the Regulation of Damaged Mitochondria Accumulation and Mitophagy Balance. Hepatology International, 8, 425-435. [Google Scholar] [CrossRef] [PubMed]
[23] Wen, Q., Chan, K.H., Shi, K., Lv, J., Guo, Y., Pei, P., et al. (2022) Tobacco Smoking and Solid Fuels for Cooking and Risk of Liver Cancer: A Prospective Cohort Study of 0.5 Million Chinese Adults. International Journal of Cancer, 151, 181-190. [Google Scholar] [CrossRef] [PubMed]
[24] Bui, T.T., Park, E., Kang, H. and Oh, J. (2024) Combined Effects of Smoking and Alcohol Consumption on the Risk of Liver Cancer According to Metabolic Syndrome: A Nested Case-Control Study in south Korea. International Journal of Cancer, 155, 654-665. [Google Scholar] [CrossRef] [PubMed]
[25] Zabala, V., Tong, M., Yu, R., Ramirez, T., Yalcin, E.B., Balbo, S., et al. (2015) Potential Contributions of the Tobacco Nicotine-Derived Nitrosamine Ketone (NNK) in the Pathogenesis of Steatohepatitis in a Chronic Plus Binge Rat Model of Alcoholic Liver Disease. Alcohol and Alcoholism, 50, 118-131. [Google Scholar] [CrossRef] [PubMed]
[26] Qin, W., Yang, Z., Li, M., Chen, Y., Zhao, X., Qin, Y., et al. (2020) High Serum Levels of Cholesterol Increase Antitumor Functions of Nature Killer Cells and Reduce Growth of Liver Tumors in Mice. Gastroenterology, 158, 1713-1727. [Google Scholar] [CrossRef] [PubMed]
[27] 陈欢, 李秀惠. 急、慢性乙型肝炎及乙肝肝硬化患者肝功能及血脂水平分析[J]. 医学信息, 2019, 32(12): 67-69.
[28] Ma, X., Cui, H., Sun, M., Liu, Q., Liu, X., Li, G., et al. (2021) Fasting Blood Glucose, Cholesterol, and Risk of Primary Liver Cancer: The Kailuan Study. Cancer Research and Treatment, 53, 1113-1122. [Google Scholar] [CrossRef] [PubMed]
[29] Sun, M., Wang, W., Liu, X., Wang, Y., Cui, H., Liu, S., et al. (2021) Total Cholesterol, Alanine Aminotransferase and the Risk of Primary Liver Cancer: A Population-Based Prospective Study. Medicine, 100, e25746. [Google Scholar] [CrossRef] [PubMed]
[30] Krautbauer, S., Weiss, T.S., Wiest, R., et al. (2017) Diagnostic Value of Systemic Cholesteryl Ester/Free Cholesterol Ratio in Hepatocellular Carcinoma. Anticancer Research, 37, 3527-3535.
[31] Solsona-Vilarrasa, E., Fucho, R., Torres, S., Nuñez, S., Nuño-Lámbarri, N., Enrich, C., et al. (2019) Cholesterol Enrichment in Liver Mitochondria Impairs Oxidative Phosphorylation and Disrupts the Assembly of Respiratory Supercomplexes. Redox Biology, 24, Article ID: 101214. [Google Scholar] [CrossRef] [PubMed]
[32] Ismail, I.T., Elfert, A., Helal, M., Salama, I., El-Said, H. and Fiehn, O. (2020) Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma. Cancers, 13, Article No. 88. [Google Scholar] [CrossRef] [PubMed]
[33] Gimm, T., Wiese, M., Teschemacher, B., Deggerich, A., Schödel, J., Knaup, K.X., et al. (2010) Hypoxia‐Inducible Protein 2 Is a Novel Lipid Droplet Protein and a Specific Target Gene of Hypoxia‐Inducible Factor‐1. The FASEB Journal, 24, 4443-4458. [Google Scholar] [CrossRef] [PubMed]
[34] 刘咏真, 康静波, 杜锐, 等. 缺氧诱导基因2甘油三酯堆积稳态失衡促进肝癌发生的研究[J]. 转化医学杂志, 2020, 9(3): 137-146.
[35] Ahn, J., Lim, U., Weinstein, S.J., Schatzkin, A., Hayes, R.B., Virtamo, J., et al. (2009) Prediagnostic Total and High-Density Lipoprotein Cholesterol and Risk of Cancer. Cancer Epidemiology, Biomarkers & Prevention, 18, 2814-2821. [Google Scholar] [CrossRef] [PubMed]
[36] Nam, S.Y., Jo, J., Lee, W.K. and Cho, C.M. (2024) Factor Modification in the Association between High-Density Lipoprotein Cholesterol and Liver Cancer Risk in a Nationwide Cohort. International Journal of Epidemiology, 53, dyae053. [Google Scholar] [CrossRef] [PubMed]
[37] Jiang, S., Weng, D., Jiang, L., Zhang, Y., Pan, K., Pan, Q., et al. (2016) The Clinical Significance of Preoperative Serum Cholesterol and High-Density Lipoprotein-Cholesterol Levels in Hepatocellular Carcinoma. Journal of Cancer, 7, 626-632. [Google Scholar] [CrossRef] [PubMed]
[38] Esteve, E., Ricart, W. and Fernández-Real, J.M. (2005) Dyslipidemia and Inflammation: An Evolutionary Conserved Mechanism. Clinical Nutrition, 24, 16-31. [Google Scholar] [CrossRef] [PubMed]
[39] Sugano, M., Tsuchida, K. and Makino, N. (2000) High-Density Lipoproteins Protect Endothelial Cells from Tumor Necrosis Factor-Α-Induced Apoptosis. Biochemical and Biophysical Research Communications, 272, 872-876. [Google Scholar] [CrossRef] [PubMed]
[40] Lupattelli, G., Marchesi, S., Lombardini, R., Siepi, D., Bagaglia, F., Pirro, M., et al. (2003) Mechanisms of High-Density Lipoprotein Cholesterol Effects on the Endothelial Function in Hyperlipemia. Metabolism, 52, 1191-1195. [Google Scholar] [CrossRef] [PubMed]
[41] Catapano, A.L., Pirillo, A., Bonacina, F. and Norata, G.D. (2014) HDL in Innate and Adaptive Immunity. Cardiovascular Research, 103, 372-383. [Google Scholar] [CrossRef] [PubMed]
[42] Menendez, J.A. and Lupu, R. (2007) Fatty Acid Synthase and the Lipogenic Phenotype in Cancer Pathogenesis. Nature Reviews Cancer, 7, 763-777. [Google Scholar] [CrossRef] [PubMed]
[43] Swinnen, J.V., Brusselmans, K. and Verhoeven, G. (2006) Increased Lipogenesis in Cancer Cells: New Players, Novel Targets. Current Opinion in Clinical Nutrition & Metabolic Care, 9, 358-365. [Google Scholar] [CrossRef] [PubMed]
[44] Nakagawa, H., Hayata, Y., Kawamura, S., Yamada, T., Fujiwara, N. and Koike, K. (2018) Lipid Metabolic Reprogramming in Hepatocellular Carcinoma. Cancers, 10, Article No. 447. [Google Scholar] [CrossRef] [PubMed]
[45] Budhu, A., Roessler, S., Zhao, X., Yu, Z., Forgues, M., Ji, J., et al. (2013) Integrated Metabolite and Gene Expression Profiles Identify Lipid Biomarkers Associated with Progression of Hepatocellular Carcinoma and Patient Outcomes. Gastroenterology, 144, 1066-1075.e1. [Google Scholar] [CrossRef] [PubMed]
[46] Cao, D., Song, X., Che, L., Li, X., Pilo, M.G., Vidili, G., et al. (2016) Both de Novo Synthetized and Exogenous Fatty Acids Support the Growth of Hepatocellular Carcinoma Cells. Liver International, 37, 80-89. [Google Scholar] [CrossRef] [PubMed]
[47] Wang, M., Wu, H., Fu, G., Zhang, H., Zhou, X., Tang, L., et al. (2016) Acetyl‐Coenzyme a Carboxylase Alpha Promotion of Glucose‐Mediated Fatty Acid Synthesis Enhances Survival of Hepatocellular Carcinoma in Mice and Patients. Hepatology, 63, 1272-1286. [Google Scholar] [CrossRef] [PubMed]
[48] Iwamoto, H., Abe, M., Yang, Y., Cui, D., Seki, T., Nakamura, M., et al. (2018) Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance. Cell Metabolism, 28, 104-117.e5. [Google Scholar] [CrossRef] [PubMed]
[49] Hu, B., Lin, J., Yang, X. and Sang, X. (2020) Aberrant Lipid Metabolism in Hepatocellular Carcinoma Cells as Well as Immune Microenvironment: A Review. Cell Proliferation, 53, e12772. [Google Scholar] [CrossRef] [PubMed]
[50] Calvisi, D.F., Wang, C., Ho, C., Ladu, S., Lee, S.A., Mattu, S., et al. (2011) Increased Lipogenesis, Induced by AKT-mTORC1-RPS6 Signaling, Promotes Development of Human Hepatocellular Carcinoma. Gastroenterology, 140, 1071-1083.e5. [Google Scholar] [CrossRef] [PubMed]
[51] Li, L., Pilo, G.M., Li, X., Cigliano, A., Latte, G., Che, L., et al. (2016) Inactivation of Fatty Acid Synthase Impairs Hepatocarcinogenesis Driven by AKT in Mice and Humans. Journal of Hepatology, 64, 333-341. [Google Scholar] [CrossRef] [PubMed]
[52] HAO, Q., LI, T., ZHANG, X., GAO, P., QIAO, P., LI, S., et al. (2014) Expression and Roles of Fatty Acid Synthase in Hepatocellular Carcinoma. Oncology Reports, 32, 2471-2476. [Google Scholar] [CrossRef] [PubMed]
[53] Ma, M.K.F., Lau, E.Y.T., Leung, D.H.W., Lo, J., Ho, N.P.Y., Cheng, L.K.W., et al. (2017) Stearoyl-COA Desaturase Regulates Sorafenib Resistance via Modulation of ER Stress-Induced Differentiation. Journal of Hepatology, 67, 979-990. [Google Scholar] [CrossRef] [PubMed]
[54] Yao, F., Bo, Y., Zhao, L., Li, Y., Ju, L., Fang, H., et al. (2021) Prevalence and Influencing Factors of Metabolic Syndrome among Adults in China from 2015 to 2017. Nutrients, 13, Article No. 4475. [Google Scholar] [CrossRef] [PubMed]