双重过氧化物酶体增殖物激活受体 α/δ 激动剂:治疗酒精相关性肝病的希望?
Dual peroxisome proliferator-activated receptor α/δ agonists: Hope for the treatment of alcohol-associated liver disease?
机构信息
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
出版信息
World J Gastroenterol. 2024 Oct 7;30(37):4163-4167. doi: 10.3748/wjg.v30.i37.4163.
In this letter, we review the article "Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease". We focus specifically on the detrimental effects of alcohol-associated liver disease (ALD) on human health. Given its insidious onset and increasing incidence, increasing awareness of ALD can contribute to reducing the prevalence of liver diseases. ALD comprises a spectrum of several different disorders, including liver steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of ALD is exceedingly complex. Previous studies have shown that peroxisome proliferator-activated receptors (PPARs) regulate lipid metabolism, glucose homeostasis and inflammatory responses within the organism. Additionally, their dysfunction is a major contributor to the progression of ALD. Elafibranor is an oral, dual PPARα and δ agonist. The effectiveness of elafibranor in the treatment of ALD remains unclear. In this letter, we emphasize the harm of ALD and the burden it places on society. Furthermore, we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets. Additionally, we discuss the mechanisms of action of PPARα and δ agonists, the significance of their antifibrotic effects on ALD and future research directions.
在这封信中,我们回顾了一篇题为“Elafibranor 对酒精性肝病小鼠模型中肝纤维化和肠道屏障功能的影响”的文章。我们特别关注酒精性肝病(ALD)对人类健康的有害影响。鉴于其隐匿性发病和发病率不断上升,提高对 ALD 的认识有助于降低肝脏疾病的患病率。ALD 包括一系列不同的疾病,包括肝脂肪变性、脂肪性肝炎、纤维化、肝硬化和肝细胞癌。ALD 的发病机制非常复杂。先前的研究表明,过氧化物酶体增殖物激活受体(PPARs)在体内调节脂质代谢、葡萄糖稳态和炎症反应。此外,它们的功能障碍是 ALD 进展的主要原因。Elafibranor 是一种口服的、双重 PPARα 和 δ 激动剂。Elafibranor 治疗 ALD 的有效性尚不清楚。在这封信中,我们强调了 ALD 的危害及其给社会带来的负担。此外,我们总结了 ALD 所有阶段的临床管理,并对其发病机制和潜在治疗靶点提出了新的见解。此外,我们还讨论了 PPARα 和 δ 激动剂的作用机制、它们对 ALD 的抗纤维化作用的意义以及未来的研究方向。
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