Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis
The pathogenesis of non-alcoholic steatohepatitis (NASH) involves the simultaneous interaction of multiple factors such as lipid accumulation, oxidative stress, and inflammatory response. Here, the effect of human serum albumin (HSA) fused to thioredoxin (Trx) on NASH was investigated. Trx is known...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024015160 |
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| author | Ryota Murata Hiroshi Watanabe Ryotaro Iwakiri Mayuko Chikamatsu Takao Satoh Isamu Noguchi Kengo Yasuda Ayano Nishinoiri Takuma Yoshitake Hiroto Nosaki Hitoshi Maeda Toru Maruyama |
| author_facet | Ryota Murata Hiroshi Watanabe Ryotaro Iwakiri Mayuko Chikamatsu Takao Satoh Isamu Noguchi Kengo Yasuda Ayano Nishinoiri Takuma Yoshitake Hiroto Nosaki Hitoshi Maeda Toru Maruyama |
| author_sort | Ryota Murata |
| collection | DOAJ |
| description | The pathogenesis of non-alcoholic steatohepatitis (NASH) involves the simultaneous interaction of multiple factors such as lipid accumulation, oxidative stress, and inflammatory response. Here, the effect of human serum albumin (HSA) fused to thioredoxin (Trx) on NASH was investigated. Trx is known to have anti-oxidative, anti-inflammatory, and anti-apoptotic effects. However, Trx is a low molecular weight protein and is rapidly eliminated from the blood. To overcome the low availability of Trx, HSA-Trx fusion protein was produced and evaluated the therapeutic effect on high-fat diet (HFD)-induced NASH model mice. HSA-Trx administered before the formation of NASH pathology showed it to have a preventive effect. Specifically, HSA-Trx was found to prevent the pathological progression to NASH by suppressing lipid accumulation, liver injury markers, and liver fibrosis. When HSA-Trx was administered during the early stage of NASH there was a marked reduction in lipid accumulation, inflammation, and fibrosis in the liver, indicating that HSA-Trx ameliorates NASH pathology. The findings indicate that HSA-Trx influences multiple pathological factors, such as oxidative stress, inflammation, and apoptosis, to elicit a therapeutic benefit. HSA-Trx also inhibited palmitic acid-induced lipotoxicity in HepG2 cells. Taken together, these results indicate that HSA-Trx has potential as a therapeutic agent for NASH pathology. |
| first_indexed | 2024-03-08T00:09:50Z |
| format | Article |
| id | doaj.art-16f005feb2354d88bb0842da67d26921 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T00:09:50Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-16f005feb2354d88bb0842da67d269212024-02-17T06:41:15ZengElsevierHeliyon2405-84402024-02-01103e25485Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitisRyota Murata0Hiroshi Watanabe1Ryotaro Iwakiri2Mayuko Chikamatsu3Takao Satoh4Isamu Noguchi5Kengo Yasuda6Ayano Nishinoiri7Takuma Yoshitake8Hiroto Nosaki9Hitoshi Maeda10Toru Maruyama11Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Corresponding author.Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanKumamoto Industrial Research Institute, Kumamoto, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, JapanThe pathogenesis of non-alcoholic steatohepatitis (NASH) involves the simultaneous interaction of multiple factors such as lipid accumulation, oxidative stress, and inflammatory response. Here, the effect of human serum albumin (HSA) fused to thioredoxin (Trx) on NASH was investigated. Trx is known to have anti-oxidative, anti-inflammatory, and anti-apoptotic effects. However, Trx is a low molecular weight protein and is rapidly eliminated from the blood. To overcome the low availability of Trx, HSA-Trx fusion protein was produced and evaluated the therapeutic effect on high-fat diet (HFD)-induced NASH model mice. HSA-Trx administered before the formation of NASH pathology showed it to have a preventive effect. Specifically, HSA-Trx was found to prevent the pathological progression to NASH by suppressing lipid accumulation, liver injury markers, and liver fibrosis. When HSA-Trx was administered during the early stage of NASH there was a marked reduction in lipid accumulation, inflammation, and fibrosis in the liver, indicating that HSA-Trx ameliorates NASH pathology. The findings indicate that HSA-Trx influences multiple pathological factors, such as oxidative stress, inflammation, and apoptosis, to elicit a therapeutic benefit. HSA-Trx also inhibited palmitic acid-induced lipotoxicity in HepG2 cells. Taken together, these results indicate that HSA-Trx has potential as a therapeutic agent for NASH pathology.http://www.sciencedirect.com/science/article/pii/S2405844024015160Albumin fusionThioredoxinNon-alcoholic fatty liver diseaseNon-alcoholic steatohepatitisOxidative stressInflammation |
| spellingShingle | Ryota Murata Hiroshi Watanabe Ryotaro Iwakiri Mayuko Chikamatsu Takao Satoh Isamu Noguchi Kengo Yasuda Ayano Nishinoiri Takuma Yoshitake Hiroto Nosaki Hitoshi Maeda Toru Maruyama Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis Heliyon Albumin fusion Thioredoxin Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Oxidative stress Inflammation |
| title | Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis |
| title_full | Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis |
| title_fullStr | Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis |
| title_full_unstemmed | Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis |
| title_short | Albumin-fused thioredoxin ameliorates high-fat diet-induced non-alcoholic steatohepatitis |
| title_sort | albumin fused thioredoxin ameliorates high fat diet induced non alcoholic steatohepatitis |
| topic | Albumin fusion Thioredoxin Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Oxidative stress Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024015160 |
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