Adipose TGR5 Deletion Promotes Hepatic Steatosis Through Decreasing Adiponectin Secretion in Mice
Systemic G-protein-coupled bile acid receptor 1 (TGR5) is involved in modulating hepatic triglyceride accumulation, but whether adipose-derived TGR5 regulates hepatic lipid metabolism remains undefined. We investigated whether fasting or a high-fat diet (HFD) altered TGR5 levels in adipose tissue and the effect of TGR5 ablation in adipose tissue on hepatic lipid metabolism. We found that TGR5 protein expression was upregulated in white adipose tissue upon fasting or HFD. Adipose-specific TGR5 deficiency decreased adiponectin secretion, which ultimately suppressed hepatic fatty acid oxidation and exacerbated intrahepatic lipid deposition. Given the limited therapeutic options for metabolic dysfunction-associated steatotic liver disease (MASLD), our findings highlight the therapeutic potential of targeting adipocyte TGR5 for MASLD intervention.
Authors
- Ying Xu (ORCID: https://orcid.org/0009-0004-6539-4431)
- Cuiyuan Huang (ORCID: https://orcid.org/0000-0002-4780-6330)
- Ying Xia (ORCID: https://orcid.org/0000-0002-0126-6594)
- Xiandan Jing
- Jinhan He (ORCID: https://orcid.org/0000-0001-6487-4696)
- Jinhang Zhang (ORCID: https://orcid.org/0000-0001-8345-614X)
- Juan Pang (ORCID: https://orcid.org/0000-0001-6272-9890)
- Yimin Xiong (ORCID: https://orcid.org/0000-0003-2736-8334)
- Yanping Li (ORCID: https://orcid.org/0000-0003-1811-0083)
- Jiahui Li (ORCID: https://orcid.org/0000-0002-9597-737X)
- Qinhui Liu (ORCID: https://orcid.org/0000-0001-9510-3704)
- Ailin Zhang (ORCID: https://orcid.org/0000-0001-9598-3772)
- Zijing Zhang (ORCID: https://orcid.org/0000-0002-3990-1442)
- Qin Tang (ORCID: https://orcid.org/0000-0001-5279-0276)
- Haiying Song (ORCID: https://orcid.org/0000-0003-4086-6194)
Institutions
- Sichuan University (CN)
- West China Hospital of Sichuan University (CN)
Publication Details
- Journal
- Diabetes
- Published
- 2025-11-26
- DOI
- https://doi.org/10.2337/db25-0344
- Citations
- 2
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- National Natural Science Foundation of China
- Sichuan University
- West China Hospital, Sichuan University