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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Main Authors: Ting HONG, Xiaoying LI
Format: Article
Language:English
Published: Shanghai Chinese Clinical Medicine Press Co., Ltd. 2025-06-01
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
collection DOAJ
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.
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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
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