Evidence map›Paper›PMID 41632920›Full record

ArticleHepatology (Baltimore, Md.)2026

Hepatic GPR75 exacerbates MASH through GNAI2-dependent signaling.

Xule Yang, Na Yang, Zhihao Cheng, Rui Zhang, Hui Fan, Dongsheng Liu, Jiye Aa, Guangji Wang, Yuan Xie

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Article in Hepatology (Baltimore, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Xule YangKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Na YangChina Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, China.
Zhihao ChengKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Rui ZhangKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Hui FanKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Dongsheng LiuKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Jiye AaKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Guangji WangKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Yuan XieKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.ORCID 0000-0002-2991-6763

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsMetabolic dysfunction-associated steatotic liver disease (MASLD), including its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), is increasingly recognized as a critical global health challenge. This study investigates the role of hepatic GPR75 in MASH progression. APPROACH AND

resultsAlthough GPR75 is not abundantly expressed in the liver in healthy individuals, its protein levels significantly increase during MASH. Depletion of Gpr75 in either the whole liver or specifically in hepatocytes protected mice from diet-induced hepatic steatosis, while hepatocyte-specific overexpression of Gpr75 exacerbated diet-induced MASH and liver fibrosis. The deficiency of hepatic Gpr75 activated the GNAI2-cAMP-PKA signaling pathway in the livers of MASLD mice, reducing SREBP-1c maturation and de novo lipogenesis. Mechanistically, VPS35 stabilized GPR75 by recycling it to the hepatocyte membrane, thereby decreasing its degradation during MASH progression.

conclusionsThis study demonstrates that GPR75 serves as a novel regulator of MASLD/MASH by modulating hepatic fatty acid metabolism. These findings suggest that GPR75 suppression may represent a potential therapeutic strategy for MASLD/MASH treatment.

Indexed as

Fatty LiverNon-alcoholic Fatty Liver DiseaseReceptors, G-Protein-CoupledAnimalsDisease Models, AnimalDisease ProgressionHepatocytesHumansLipogenesisLiverMaleMiceSignal TransductionVesicular Transport ProteinsReceptors, G-Protein-CoupledSUCNR1 protein, humanVesicular Transport Proteinsde novo lipogenesisGNAI2GPR75MASHVPS35

Identifiers

PMID41632920
PMCPMC13668042

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.