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高脂/高果糖饮食和华支睾吸虫感染通过炎症、纤维化和代谢功能障碍促进代谢功能障碍相关脂肪性肝病。

High-fat/high-fructose diet and Opisthorchis viverrini infection promote metabolic dysfunction-associated steatotic liver disease via inflammation, fibrogenesis, and metabolic dysfunction.

作者信息

Charoensuk Lakhanawan, Thongpon Phonpilas, Sitthirach Chutima, Chaidee Apisit, Intuyod Kitti, Pairojkul Chawalit, Khin Ei Htet Htet, Jantawong Chanakan, Thumanu Kanjana, Pinlaor Porntip, Hongsrichan Nuttanan, Pinlaor Somchai

机构信息

Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Thailand.

Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Thailand.

出版信息

Acta Trop. 2025 Jan;261:107491. doi: 10.1016/j.actatropica.2024.107491. Epub 2024 Dec 4.

DOI:10.1016/j.actatropica.2024.107491
PMID:39643028
Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) and opisthorchiasis, caused by Opisthorchis viverrini (O. viverrini) infection, frequently co-exist in Northeast Thailand. However, the underlying pathophysiology remains unknown. We aimed to investigate the effect of a high-fat/high-fructose (HFF) diet combined with O. viverrini infection on MASLD. Four groups each of ten male golden hamsters were established: normal controls (NC), O. viverrini-infected (OV), HFF-fed, and HFF-fed plus O. viverrini infection (HFF+OV). After four months of treatment, histopathological study indicated substantial hepatic damage in groups given the HFF diet. In particular, the HFF+OV group demonstrated marked lipid-droplet accumulation, hepatocyte ballooning, inflammatory-cell clustering, and widespread fibrosis. Biochemical tests indicated that the HFF+OV group had the highest concentrations of alanine aminotransferase and triglycerides, but cholesterol and low-density lipoprotein levels had increased in both HFF groups. Increased expression of Tgf-β1 and α-SMA, indicative of greater fibrosis, was demonstrated by picrosirius-red staining in the HFF+OV group. There was a significant increase in levels of inflammatory markers (HMGB-1, p65, and F4/80) and expression of genes related to the synthesis of fatty acids and glucose. FTIR microspectroscopy revealed distinct changes in fatty acids and proteins, associated with the more pronounced histopathology and impaired liver function in the HFF+OV group. The findings indicate that the interplay of a HFF diet and O. viverrini infection aggravates the progression of MASLD by augmenting liver damage, inflammation, fibrogenesis, and metabolic dysfunction. This study highlights the significance of incorporating both nutritional and infection factors into the management of liver disorders, especially in areas where opisthorchiasis is common.

摘要

代谢功能障碍相关脂肪性肝病(MASLD)与由麝猫后睾吸虫(O. viverrini)感染引起的后睾吸虫病,在泰国东北部经常同时存在。然而,其潜在的病理生理学机制仍不清楚。我们旨在研究高脂/高果糖(HFF)饮食联合O. viverrini感染对MASLD的影响。将40只雄性金黄仓鼠分为四组,每组10只:正常对照组(NC)、O. viverrini感染组(OV)、HFF喂养组和HFF喂养加O. viverrini感染组(HFF+OV)。治疗四个月后,组织病理学研究表明,给予HFF饮食的组肝脏损伤严重。特别是,HFF+OV组表现出明显的脂滴积聚、肝细胞气球样变、炎症细胞聚集和广泛纤维化。生化检测表明,HFF+OV组丙氨酸转氨酶和甘油三酯浓度最高,但两个HFF组的胆固醇和低密度脂蛋白水平均有所升高。HFF+OV组经苦味酸天狼星红染色显示Tgf-β1和α-SMA表达增加,提示纤维化程度加重。炎症标志物(HMGB-1、p65和F4/80)水平及与脂肪酸和葡萄糖合成相关基因的表达显著增加。傅里叶变换红外光谱显微镜分析显示,脂肪酸和蛋白质有明显变化,这与HFF+OV组更明显的组织病理学改变和肝功能受损有关。研究结果表明,HFF饮食与O. viverrini感染的相互作用通过加重肝损伤、炎症、纤维化和代谢功能障碍,加速了MASLD的进展。本研究强调了在肝脏疾病管理中纳入营养和感染因素的重要性,特别是在后睾吸虫病常见的地区。

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