Abstract: TH-PO943
Environmental Circadian Disruption Accelerates 5/6 Nephrectomy-Induced Chronic Kidney Injury in Mice
Session Information
- Health Maintenance, Nutrition, Metabolism - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Chen, Lihong, Dalian Medical University, Dalian, Liaoning, China
- Zhang, Jiayang, Dalian Medical University, Dalian, Liaoning, China
- Yang, Guangrui, Shanghai University of Medicine and Health Sciences, Shanghai, -- None selected --, China
Background
Circadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with many metabolic disorders. The effect and mechanism of circadian disruption on renal injury and chronic kidney disease (CKD) remains poorly understood.Here, we evaluated the effect of environmental light/dark shifting on the progression of chronic renal injury in CKD mice.
Methods
Mice were subjected to 5/6 nephrectomy and then exposed to either a standard 12h light/12h dark (12L/12D) cycle or weekly light-dark cycle reverse (LDDL) or weekly 6h phase advance (6h advance) for 3 months. Plasma and kidney tissues were harvested for renal function and histological examination. RNA-seq and untargeted metabolomics were performed for mechanistic investigation.
Results
The results showed that 3-month light interference by weekly LDDL significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy, while light interference by weekly 6h phase advance failed to worsen renal function and kidney injury. RNA-seq and untargeted metabolomics results revealed significant upregulation of genes related to inflammatory response and immune cell chemotaxis, while obvious downregulation of genes and metabolites related to energy metabolism was indicated in the LDDL-conditioned CKD kidneys. Consistently, the renal content of ATP was decreased and ROS production was increased in the residual kidney tissues of the LDDL-challenged CKD mice.
Conclusion
We concluded that circadian disruption by environmental light interference may aggravate chronic kidney injury by facilitating inflammatory response and suppressing energy metabolism in the CKD kidneys. Targeting the circadian machinery and keeping routine light-dark cycles may represent promising approaches for the prevention and treatment of CKD.