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乳酸及乳酸代谢在肝脏疾病中的作用(综述)。

Role of lactate and lactate metabolism in liver diseases (Review).

机构信息

Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.

Department of Burns and Plastic Surgery, Fuling Hospital, Chongqing University, Chongqing 408099, P.R. China.

出版信息

Int J Mol Med. 2024 Jul;54(1). doi: 10.3892/ijmm.2024.5383. Epub 2024 May 24.

Abstract

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

摘要

乳酸是糖酵解的副产物,在发现瓦博格效应(即在有氧条件下葡萄糖可以发酵产生乳酸)之前,它被认为是一种代谢废物。目前,乳酸不仅被认为是提供能量的代谢底物,还被认为是一种信号分子,在病理生理条件下调节细胞功能。乳酸化是一种翻译后修饰,参与了多种疾病的发生,包括炎症和肿瘤。肝脏疾病是全球范围内的主要健康挑战。在正常肝脏中,由于糖异生作用会导致净乳酸摄取,其净乳酸清除率高于任何其他器官。因此,乳酸和乳酸代谢的异常会导致肝脏疾病的发生,而与乳酸和乳酸代谢相关的基因可用于预测肝脏疾病的预后。靶向乳酸生成、调节乳酸转运和调节乳酸化可能是肝脏疾病的潜在治疗方法。然而,目前尚无系统综述总结乳酸和乳酸代谢在肝脏疾病中的作用。本综述总结了乳酸和乳酸代谢在肝纤维化、非酒精性脂肪性肝病、急性肝衰竭和肝细胞癌等肝脏疾病中的作用,旨在为未来的研究提供思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10ff/11188982/236a061f2a7b/ijmm-54-01-05383-g00.jpg

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