Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice
Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease (NAFLD) and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group (Chow group) and a methionine-choline-deficient (MCD)...
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Editorial Office of Journal of Shanghai Jiao Tong University (Medical Science)
2025-04-01
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| Series: | Shanghai Jiaotong Daxue xuebao. Yixue ban |
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| Online Access: | https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-4-415.shtml |
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| author | WANG Renjie ZHU Chaoyu FANG Yunyun XIAO Yuanyuan WANG Qianqian SONG Wenjing WEI Li |
| author_facet | WANG Renjie ZHU Chaoyu FANG Yunyun XIAO Yuanyuan WANG Qianqian SONG Wenjing WEI Li |
| author_sort | WANG Renjie |
| collection | DOAJ |
| description | Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease (NAFLD) and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group (Chow group) and a methionine-choline-deficient (MCD) diet group (MCD group), with 10 mice per group. The MCD diet was used to induce NAFLD. Each group was further divided into two subgroups, resulting in four subgroups: Chow+saline, Chow+liraglutide, MCD+saline, and MCD+liraglutide group. After daily intraperitoneal injection of liraglutide (400 μg/kg) or an equivalent volume of saline for 4 weeks, an intraperitoneal glucose tolerance test (IPGTT) was performed. Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TAG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Liver tissues were collected post-euthanasia to assess TAG content. Histopathological changes, lipid deposition, and fibrosis were evaluated via hematoxylin-eosin (HE) staining, Oil Red O staining, and Masson staining. Real-time quantitative PCR (qPCR) and Western blotting were used to analyze the expression of α-smooth muscle actin (α-SMA), fibronectin (FN), collagen type Ⅰ α (COL1A), matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1 (TIMP1), transforming growth factor β (TGF-β), SMAD3, and phosphorylated SMAD3 (pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15, 30, and 60 min, with a decreased area under the curve (AUC) (both P<0.05). Biochemical analysis showed that liraglutide lowered AST and ALT levels (both P<0.001), increased TC and HDL-C levels (both P<0.05), but had no significant effect on TAG or LDL-C in MCD mice. HE staining and Oil Red O staining revealed reduced lipid droplets, ballooning degeneration, and inflammatory infiltration in hepatocytes after liraglutide treatment. Masson staining indicated decreased collagen fiber deposition in the liver. qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA, FN, COL1A, TIMP1, TGF-β, and pSMAD3/SMAD3, alongside downregulated MMP9 in MCD mice. Liraglutide reversed these changes, lowering α-SMA, FN, COL1A, TIMP1, TGF-β, and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury, lipid deposition, and fibrosis in NAFLD mice, through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression. |
| format | Article |
| id | doaj-art-e2ca268637ad41a5acff330c8652a841 |
| institution | OA Journals |
| issn | 1674-8115 |
| language | zho |
| publishDate | 2025-04-01 |
| publisher | Editorial Office of Journal of Shanghai Jiao Tong University (Medical Science) |
| record_format | Article |
| series | Shanghai Jiaotong Daxue xuebao. Yixue ban |
| spelling | doaj-art-e2ca268637ad41a5acff330c8652a8412025-08-20T01:55:31ZzhoEditorial Office of Journal of Shanghai Jiao Tong University (Medical Science)Shanghai Jiaotong Daxue xuebao. Yixue ban1674-81152025-04-0145441542510.3969/j.issn.1674-8115.2025.04.0031674-8115（2025）04-0415-11Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD miceWANG Renjie0ZHU Chaoyu1FANG Yunyun2XIAO Yuanyuan3WANG Qianqian4SONG Wenjing5WEI Li6College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Endocrinology and Metabolism, Shanghai Sixth People´s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Sixth People´s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Sixth People´s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Sixth People´s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Sixth People´s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Sixth People´s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, ChinaObjective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease (NAFLD) and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group (Chow group) and a methionine-choline-deficient (MCD) diet group (MCD group), with 10 mice per group. The MCD diet was used to induce NAFLD. Each group was further divided into two subgroups, resulting in four subgroups: Chow+saline, Chow+liraglutide, MCD+saline, and MCD+liraglutide group. After daily intraperitoneal injection of liraglutide (400 μg/kg) or an equivalent volume of saline for 4 weeks, an intraperitoneal glucose tolerance test (IPGTT) was performed. Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TAG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Liver tissues were collected post-euthanasia to assess TAG content. Histopathological changes, lipid deposition, and fibrosis were evaluated via hematoxylin-eosin (HE) staining, Oil Red O staining, and Masson staining. Real-time quantitative PCR (qPCR) and Western blotting were used to analyze the expression of α-smooth muscle actin (α-SMA), fibronectin (FN), collagen type Ⅰ α (COL1A), matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1 (TIMP1), transforming growth factor β (TGF-β), SMAD3, and phosphorylated SMAD3 (pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15, 30, and 60 min, with a decreased area under the curve (AUC) (both P<0.05). Biochemical analysis showed that liraglutide lowered AST and ALT levels (both P<0.001), increased TC and HDL-C levels (both P<0.05), but had no significant effect on TAG or LDL-C in MCD mice. HE staining and Oil Red O staining revealed reduced lipid droplets, ballooning degeneration, and inflammatory infiltration in hepatocytes after liraglutide treatment. Masson staining indicated decreased collagen fiber deposition in the liver. qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA, FN, COL1A, TIMP1, TGF-β, and pSMAD3/SMAD3, alongside downregulated MMP9 in MCD mice. Liraglutide reversed these changes, lowering α-SMA, FN, COL1A, TIMP1, TGF-β, and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury, lipid deposition, and fibrosis in NAFLD mice, through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-4-415.shtmlliraglutidetransforming growth factor-β (tgf-β)sma- and mad-related protein 3 (smad3)non-alcoholic fatty liver diseaseliver fibrosis |
| spellingShingle | WANG Renjie ZHU Chaoyu FANG Yunyun XIAO Yuanyuan WANG Qianqian SONG Wenjing WEI Li Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice Shanghai Jiaotong Daxue xuebao. Yixue ban liraglutide transforming growth factor-β (tgf-β) sma- and mad-related protein 3 (smad3) non-alcoholic fatty liver disease liver fibrosis |
| title | Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice |
| title_full | Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice |
| title_fullStr | Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice |
| title_full_unstemmed | Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice |
| title_short | Effects and mechanisms of liraglutide in ameliorating liver fibrosis in NAFLD mice |
| title_sort | effects and mechanisms of liraglutide in ameliorating liver fibrosis in nafld mice |
| topic | liraglutide transforming growth factor-β (tgf-β) sma- and mad-related protein 3 (smad3) non-alcoholic fatty liver disease liver fibrosis |
| url | https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-4-415.shtml |
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