Hepatic GPR110 plays a complex and context-dependent role in metabolic dysfunction-associated steatotic liver disease
Metabolically-dysfunction-associated steatotic liver disease (MASLD)—formerly known as nonalcoholic fatty liver disease (NAFLD) —is now the most common chronic liver disease worldwide, affecting more than 30% of the global population. Recent studies have documented seemingly contradictory roles for the G protein-coupled receptor 110 (GPR110, also known as ADGRF1) in male-biased models of MASLD. Here, we synthesize these findings and propose that such discrepancies do not invalidate the new discoveries but rather underscore the profound context‑dependency of GPR110 biology. We outline a multidimensional framework wherein the net effect of GPR110 signaling is dictated by sex hormones and their receptors, disease stage (simple steatosis vs . steatohepatitis/fibrosis), and the cell type-specific signaling plasticity of this G protein-coupled receptor. By critically appraising experimental designs, model limitations, incomplete hormonal characterization, and potential confounders, we highlight key considerations for translational research. Ultimately, we emphasize that precise, context-informed strategies will be critical for therapeutically targeting GPR110-mediated pathways across a heterogeneous patient population.
Authors
- Yongguo Dai (ORCID: https://orcid.org/0000-0002-9023-5211)
- Yueping Jiang (ORCID: https://orcid.org/0000-0002-5820-0123)
- Chao Huang (ORCID: https://orcid.org/0000-0003-1186-0973)
- Hanwen Gu (ORCID: https://orcid.org/0000-0002-2716-9055)
- Xufeng Li (ORCID: https://orcid.org/0000-0002-2666-3502)
- Xiaoping Chen (ORCID: https://orcid.org/0000-0002-2910-9152)
- Shao Liu (ORCID: https://orcid.org/0000-0002-0576-8698)
- Qiming Liu (ORCID: https://orcid.org/0000-0003-0282-4313)
Institutions
- Ningbo University (CN)
- Fujian Medical University (CN)
- Central South University (CN)
- Ningbo Medical Center Lihuili Hospital (CN)
- Hunan Academy of Traditional Chinese Medicine (CN)
- National Clinical Research (US)
- Second Affiliated Hospital of Fujian Medical University (CN)
- Second Xiangya Hospital of Central South University (CN)
- Xiangya Hospital Central South University (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- npj gut and liver.
- Published
- 2026-08-03
- DOI
- https://doi.org/10.1038/s44355-026-00077-9
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Shandong University
- Qilu Hospital of Shandong University
- National Natural Science Foundation of China
- Central South University
- China Postdoctoral Science Foundation
- Government of Jiangsu Province
- Natural Science Foundation of Fujian Province
- Ningbo University
- Natural Science Foundation of Hunan Province
- Nanjing Medical University
- Fujian Medical University
- National Health Commission of the People's Republic of China
- Science and Technology Program of Hunan Province
- Xiangya Hospital, Central South University