肝脏腐胺水平升高是与代谢功能障碍相关性脂肪性肝病进展有关的一个新的潜在因素。

IF 5.6 2区 医学 Q1 ONCOLOGY The Journal of Pathology Pub Date : 2024-07-18 DOI:10.1002/path.6330
María Ángeles Núñez-Sánchez, María Antonia Martínez-Sánchez, Marta Sierra-Cruz, Ana Lambertos, Sara Rico-Chazarra, Alba Oliva-Bolarín, Andrés Balaguer-Román, José Enrique Yuste, Carlos Manuel Martínez, Adriana Mika, María Dolores Frutos, Camilo J Llamoza-Torres, José Córdoba-Chacón, Bruno Ramos-Molina
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引用次数: 0

摘要

代谢功能障碍相关性脂肪性肝病(MASLD)是一种慢性肝病,通常会发展到晚期,如代谢功能障碍相关性脂肪性肝炎(MASH)。除肝脏脂肪变性外,MASH 还以炎症和肝细胞气球化为特征。尽管 MASH 在人群中的发病率相对较高,而且对人类健康有潜在的不利影响,但从病理生理学的角度来看,人们对这种肝病的了解仍不全面。在神经退行性疾病、炎症和癌症等各种病理情况中都发现了多胺水平的失调。然而,多胺通路在慢性肝脏疾病(如 MASLD)中的作用尚未得到探讨。在这项研究中,我们测定了肝脏鸟氨酸脱羧酶(ODC1)的表达(ODC1是负责产生腐胺的限速酶)以及肝脏中腐胺的水平。我们的研究结果表明,与对照组小鼠和非 MASH 患者相比,饮食诱导的 MASH 小鼠和活检证实的 MASH 患者的肝组织中,ODC1 的表达和腐胺酸的水平都有所升高,但亚精胺和精胺的水平却没有升高。此外,我们还发现腐胺酸水平与血清中较高的天冬氨酸氨基转移酶浓度和 SAF 评分(脂肪变性、活动性、纤维化)的增加呈正相关。此外,在使用人 HepG2 细胞进行的体外试验中,我们证明腐胺水平升高会加剧细胞对棕榈酸的反应,导致细胞活力下降和 CK-18 释放增加。我们的研究结果支持 ODC1 的表达与 MASLD 的进展之间存在关联,这可能对理解这种疾病的发病具有转化意义。© 2024 大不列颠及爱尔兰病理学会。
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Increased hepatic putrescine levels as a new potential factor related to the progression of metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition that often progresses to more advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH). MASH is characterized by inflammation and hepatocellular ballooning, in addition to hepatic steatosis. Despite the relatively high incidence of MASH in the population and its potential detrimental effects on human health, this liver disease is still not fully understood from a pathophysiological perspective. Deregulation of polyamine levels has been detected in various pathological conditions, including neurodegenerative diseases, inflammation, and cancer. However, the role of the polyamine pathway in chronic liver disorders such as MASLD has not been explored. In this study, we measured the expression of liver ornithine decarboxylase (ODC1), the rate-limiting enzyme responsible for the production of putrescine, and the hepatic levels of putrescine, in a preclinical model of MASH as well as in liver biopsies of patients with obesity undergoing bariatric surgery. Our findings reveal that expression of ODC1 and the levels of putrescine, but not spermidine nor spermine, are elevated in hepatic tissue of both diet-induced MASH mice and patients with biopsy-proven MASH compared with control mice and patients without MASH, respectively. Furthermore, we found that the levels of putrescine were positively associated with higher aspartate aminotransferase concentrations in serum and an increased SAF score (steatosis, activity, fibrosis). Additionally, in in vitro assays using human HepG2 cells, we demonstrate that elevated levels of putrescine exacerbate the cellular response to palmitic acid, leading to decreased cell viability and increased release of CK-18. Our results support an association between the expression of ODC1 and the progression of MASLD, which could have translational relevance in understanding the onset of this disease. © 2024 The Pathological Society of Great Britain and Ireland.

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来源期刊
The Journal of Pathology
The Journal of Pathology 医学-病理学
CiteScore
14.10
自引率
1.40%
发文量
144
审稿时长
3-8 weeks
期刊介绍: The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.
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