Abstract: TH-PO0805
α-Ketoglutarate Modulates Lipid Metabolism to Ameliorate Kidney Injury in Mice with Chronic Heart Failure
Session Information
- CKM Axis: Vascular Dysfunction, Atherosclerosis, and Heart Failure in Kidney Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Authors
- Yu, Hao, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Han, Qianqian, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Wei, Xiaona, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Li, Jiajia, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Yang, Qiongqiong, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
Background
Metabolic reprogramming serves as a potential bridge connecting cardiac and renal injury, contributing to the mutual damage between the heart and kidneys. α-Ketoglutarate (AKG) is a cellular energy metabolite. Previous studies have found that AKG supplementation alleviates myocardial hypertrophy and fibrosis and improves cardiac dysfunction in mice with chronic heart failure (CHF). Renal tubular epithelial cells and cardiomyocytes share similar energy metabolism processes. Whether AKG supplementation can ameliorate kidney injury following CHF remains unknown.
Methods
6-week-old male C57 mice underwent transverse aortic constriction (TAC) surgery to establish a CHF model. The mice were treated with 2%AKG added to diet post-surgery. At 10 weeks post-surgery, cardiac function was assessed by echocardiography, renal injury was evaluated histologically, and non-targeted metabolomics was performed to detect metabolic changes in kidney tissue, to investigate whether AKG supplementation exerts renal protective effects and the underlying mechanisms.
Results
(1) Echocardiography indicated that at 10 weeks post-surgery, AKG supplementation improved left ventricular ejection fraction and protected cardiac function. (2) Histological staining revealed that AKG supplementation alleviated renal inflammatory cell infiltration and interstitial fibrosis induced by CHF; additionally, lipid peroxidation in renal tubular cells after heart failure was ameliorated by AKG treatment. (3) Non-targeted metabolomics analysis of mouse kidney tissue showed that dietary AKG supplementation significantly altered kidney metabolism in mice with CHF, including lipid metabolism, glucose metabolism, and amino acid metabolism, among which changes in lipid metabolism pathways were the most pronounced. Furthermore, similar metabolomic changes were observed in the sham and sham+AKG groups. This suggests that the effect of AKG on kidney metabolism is independent of its cardiac protective effects, and AKG may exert renal protection by modulating renal lipid metabolism.
Conclusion
This study demonstrates that AKG supplementation ameliorates cardiac and renal injury in TAC mice, likely through the regulation of renal cellular metabolism, particularly lipid metabolism pathways.
Acknowledgment
Funding: This work was supported by National Natural Science Foundation of China [82400856, 82270743, 82200822], National Key Research and Development Program of China [2024YFC3607400], GuangDong Basic and Applied Basic Research Foundation [2024A1515220083].
Funding
- Government Support – Non-U.S.