Repurposing of the analgesic Neurotropin for MASLD/MASH treatment.

IF 5.6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hepatology Communications Pub Date : 2024-07-18 eCollection Date: 2024-08-01 DOI:10.1097/HC9.0000000000000480
Takashi Tsuchiya, So Yeon Kim, Michitaka Matsuda, Jieun Kim, Alexsandr Stotland, Mitsuru Naiki, Ekihiro Seki
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引用次数: 0

Abstract

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased in recent decades. Approximately 25% of patients with MASLD progress to metabolic dysfunction-associated steatohepatitis, which is characterized by hepatic steatosis plus hepatocyte damage, inflammation, and fibrosis. We previously reported that Neurotropin (NTP), a drug used for relieving pain in Japan and China, inhibits lipid accumulation in hepatocytes by preventing mitochondrial dysfunction. We hypothesized that inhibiting hepatic steatosis and inflammation by NTP can be an effective strategy for treating MASLD and tested this hypothesis in a MASLD mouse model.

Methods: Six-week-old C57BL/6NJ male mice were fed a normal diet and normal drinking water or a high-fat diet with high fructose/glucose water for 12 weeks. During the last 6 weeks, the mice were also given high-dose NTP, low-dose NTP, or control treatment. Histologic, biochemical, and functional tests were conducted. MitoPlex, a new proteomic platform, was used to measure mitochondrial proteins, as mitochondrial dysfunction was previously reported to be associated with MASLD progression.

Results: NTP inhibited the development of hepatic steatosis, injury, inflammation, and fibrosis induced by feeding a high-fat diet plus high fructose/glucose in drinking water. NTP also inhibited HSC activation. MitoPlex analysis revealed that NTP upregulated the expression of mitochondrial proteins related to oxidative phosphorylation, the tricarboxylic acid cycle, mitochondrial dynamics, and fatty acid transport.

Conclusions: Our results indicate that NTP prevents the development of hepatic steatosis, injury, and inflammation by preserving mitochondrial function in the liver and inhibits liver fibrosis by suppressing HSC activation. Thus, repurposing NTP may be a beneficial option for treating MASLD/metabolic dysfunction-associated steatohepatitis.

将镇痛药神经促肾上腺皮质激素重新用于治疗 MASLD/MASH。
背景:近几十年来,代谢功能障碍相关性脂肪性肝病(MASLD)的发病率有所上升。大约 25% 的代谢功能障碍相关性脂肪性肝炎患者会发展为代谢功能障碍相关性脂肪性肝炎,其特点是肝脏脂肪变性加上肝细胞损伤、炎症和纤维化。我们以前曾报道过,在日本和中国用于缓解疼痛的药物神经促肾上腺皮质激素(NTP)可通过防止线粒体功能障碍来抑制肝细胞中的脂质积累。我们推测,通过NTP抑制肝脏脂肪变性和炎症可能是治疗MASLD的有效策略,并在MASLD小鼠模型中测试了这一假设:6周大的C57BL/6NJ雄性小鼠以正常饮食和正常饮用水或高脂肪饮食加高果糖/葡萄糖水喂养12周。在最后 6 周,小鼠还接受了高剂量 NTP、低剂量 NTP 或对照组治疗。对小鼠进行了组织学、生化和功能测试。MitoPlex是一种新的蛋白质组学平台,用于测量线粒体蛋白质,因为线粒体功能障碍以前曾被报道与MASLD的进展有关:结果:NTP抑制了高脂饮食和高果糖/葡萄糖饮水诱发的肝脏脂肪变性、损伤、炎症和纤维化。NTP 还能抑制造血干细胞的活化。MitoPlex分析显示,NTP上调了与氧化磷酸化、三羧酸循环、线粒体动力学和脂肪酸转运相关的线粒体蛋白的表达:我们的研究结果表明,NTP 通过保护肝脏线粒体功能防止肝脏脂肪变性、损伤和炎症的发生,并通过抑制造血干细胞活化抑制肝纤维化。因此,重新利用 NTP 可能是治疗 MASLD/代谢功能障碍相关性脂肪性肝炎的有益选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hepatology Communications
Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
8.00
自引率
2.00%
发文量
248
审稿时长
8 weeks
期刊介绍: Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction. ​
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