Abstract: SA-PO0496
Dapagliflozin Ameliorates Obesity-Induced Renal Sodium Handling Dysfunction via Inhibition of IL-6/STAT3 Signaling
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Zhao, Shasha, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Cai, Jiahui, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Sun, Feifei, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Sun, Yunbo, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Pan, Qiaoyun, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Yang, Feng, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Tan, Runyan, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Dong, Fengxiao, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Liu, Weiping, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China
- Pierre, Sandrine V., Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, West Virginia, United States
- Yan, Yanling, Key Labs Nanobiotech & Applied Chemistry, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
Group or Team Name
- S&T Program of Hebei and Hebei Provincial Department of Human Resources and Social Security.
Background
The sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin (Dapa) exhibits renal protective properties in metabolic disorders. However, the underlying mechanisms remain incompletely understood. This study investigates the role of IL-6/STAT3 signaling in obesity-induced impairment of renal sodium handling and the therapeutic potential of Dapa.
Methods
Diet-induced obese (DIO) C57BL/6J mice were used to assess the effects of Dapa on renal IL-6/Stat3 signaling and sodium excretion in response to a high-salt challenge. In vitro mechanistic studies were performed in human (HK-2) and pig (LLC-PK1) renal proximal tubular cells. The phosphorylation status of STAT3 and ERK1/2 following IL-6 stimulation, with or without Dapa or the SRC inhibitor PP2, was analyzed by immunoblotting.
Results
IL-6/Stat3 signaling was markedly activated in the renal cortex tissues of DIO mice. Obese mice exhibited significantly impaired sodium excretion under high-salt conditions compared to lean controls. Dapa treatment suppressed renal IL-6/Stat3 activation and restored natriuretic responsiveness. In HK-2 and LLC-PK1 cells, Dapa inhibited IL-6-induced phosphorylation of ERK1/2 and Stat3. Similarly, the SRC kinase inhibitor PP2 attenuated IL-6-mediated ERK1/2 and Stat3 activation (Figure 1), suggesting a shared upstream pathway.
Conclusion
These findings highlight a pivotal role of IL-6/STAT3 signaling in mediating obesity-related renal sodium handling defects. Dapagliflozin confers renoprotection by suppressing this pro-inflammatory signaling cascade. Targeting IL-6/STAT3 may represent a novel therapeutic approach for obesity-associated renal dysfunction.
Figure 1. The impact of dapagliflozin on IL-6/Stat3 signaling
Funding
- NIDDK Support