Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis
ObjectiveTo investigate expression changes and regulatory roles of adhesion G protein-coupled receptor F1 (ADGRF1/GPR110) in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatic fibrosis. MethodsHuman MASH liver tissues were collected for GPR110 detection via real-time quantitativ...
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Shanghai Chinese Clinical Medicine Press Co., Ltd.
2025-06-01
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| Series: | Zhongguo Linchuang Yixue |
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| Online Access: | https://www.c-jcm.com/article/doi/10.12025/j.issn.1008-6358.2025.20250388 |
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| author | Ting HONG Xiaoying LI |
| author_facet | Ting HONG Xiaoying LI |
| author_sort | Ting HONG |
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| description | ObjectiveTo investigate expression changes and regulatory roles of adhesion G protein-coupled receptor F1 (ADGRF1/GPR110) in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatic fibrosis. MethodsHuman MASH liver tissues were collected for GPR110 detection via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Eight-week-old male C57BL/6 mice were randomly divided into four groups: control+AAV-GFP group, control+AAV-GPR110 group, MASH+AAV-GFP group, and MASH+AAV-GPR110 group. MASH was induced by high-fat with high-sucrose diet and low-dose CCl4 intraperitoneal injections, with AAV-GPR110/AAV-GFP delivered via tail vein. Liver tissues were harvested at designated intervals (4 w, 8 w, and 12 w). Western blotting measured GPR110 expression; hematoxylin-eosin and oil red O staining assessed histology and lipid content; F4/80 and α-smooth muscle actin (α-SMA) immunofluorescence staining evaluated inflammation and fibrosis; qRT-PCR quantified hepatic expression of lipid metabolism, inflammatory, and fibrotic genes. ResultsGPR110 expression was significantly reduced in livers of MASH patients compared with controls (P<0.05). MASH+AAV-GPR110 mice exhibited lower weight, liver index, and serum lipids compared with MASH+AAV-GFP (P<0.05). Lipid synthesis-related gene (SCD-1), lipid uptake-related gene (CD36), gluconeogenesis-related genes (PEPCK and G-6-Pase), and inflammation-related genes (TNF-α, NF-κB, and iNOS) in liver were downregulated in MASH+AAV-GPR110 (P<0.05). Hepatic F4/80+ and α-SMA+ areas decreased in MASH+AAV-GPR110 (P<0.05). ConclusionGPR110 overexpression ameliorates hepatic lipid accumulation, reduces inflammation, and delays fibrosis in MASH. |
| format | Article |
| id | doaj-art-1870bcf649014bd7835e93079a09fb15 |
| institution | Kabale University |
| issn | 1008-6358 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Shanghai Chinese Clinical Medicine Press Co., Ltd. |
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| series | Zhongguo Linchuang Yixue |
| spelling | doaj-art-1870bcf649014bd7835e93079a09fb152025-08-20T03:28:51ZengShanghai Chinese Clinical Medicine Press Co., Ltd.Zhongguo Linchuang Yixue1008-63582025-06-0132333434110.12025/j.issn.1008-6358.2025.2025038820250388Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitisTing HONG0Xiaoying LI1Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 230032, ChinaDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 230032, ChinaObjectiveTo investigate expression changes and regulatory roles of adhesion G protein-coupled receptor F1 (ADGRF1/GPR110) in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatic fibrosis. MethodsHuman MASH liver tissues were collected for GPR110 detection via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Eight-week-old male C57BL/6 mice were randomly divided into four groups: control+AAV-GFP group, control+AAV-GPR110 group, MASH+AAV-GFP group, and MASH+AAV-GPR110 group. MASH was induced by high-fat with high-sucrose diet and low-dose CCl4 intraperitoneal injections, with AAV-GPR110/AAV-GFP delivered via tail vein. Liver tissues were harvested at designated intervals (4 w, 8 w, and 12 w). Western blotting measured GPR110 expression; hematoxylin-eosin and oil red O staining assessed histology and lipid content; F4/80 and α-smooth muscle actin (α-SMA) immunofluorescence staining evaluated inflammation and fibrosis; qRT-PCR quantified hepatic expression of lipid metabolism, inflammatory, and fibrotic genes. ResultsGPR110 expression was significantly reduced in livers of MASH patients compared with controls (P<0.05). MASH+AAV-GPR110 mice exhibited lower weight, liver index, and serum lipids compared with MASH+AAV-GFP (P<0.05). Lipid synthesis-related gene (SCD-1), lipid uptake-related gene (CD36), gluconeogenesis-related genes (PEPCK and G-6-Pase), and inflammation-related genes (TNF-α, NF-κB, and iNOS) in liver were downregulated in MASH+AAV-GPR110 (P<0.05). Hepatic F4/80+ and α-SMA+ areas decreased in MASH+AAV-GPR110 (P<0.05). ConclusionGPR110 overexpression ameliorates hepatic lipid accumulation, reduces inflammation, and delays fibrosis in MASH.https://www.c-jcm.com/article/doi/10.12025/j.issn.1008-6358.2025.20250388adhesion g protein-coupled receptor f1metabolic dysfunction-associated steatohepatitislipid metabolismhepatic fibrosis |
| spellingShingle | Ting HONG Xiaoying LI Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis Zhongguo Linchuang Yixue adhesion g protein-coupled receptor f1 metabolic dysfunction-associated steatohepatitis lipid metabolism hepatic fibrosis |
| title | Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis |
| title_full | Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis |
| title_fullStr | Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis |
| title_full_unstemmed | Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis |
| title_short | Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis |
| title_sort | expression changes and functional role of gpr110 in metabolic dysfunction associated steatohepatitis |
| topic | adhesion g protein-coupled receptor f1 metabolic dysfunction-associated steatohepatitis lipid metabolism hepatic fibrosis |
| url | https://www.c-jcm.com/article/doi/10.12025/j.issn.1008-6358.2025.20250388 |
| work_keys_str_mv | AT tinghong expressionchangesandfunctionalroleofgpr110inmetabolicdysfunctionassociatedsteatohepatitis AT xiaoyingli expressionchangesandfunctionalroleofgpr110inmetabolicdysfunctionassociatedsteatohepatitis |