Kidney Week

Abstract: FR-PO257

Liquid Chromatography Tandem Mass Spectrometry Analysis of Lipidomic Differences between Renal Cortex and Medulla in db/db Mice

Session Information

• Diabetic Kidney Disease: Basic - 1
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 701 Diabetic Kidney Disease: Basic

Authors

• Lim, Hyun Ji, Kyung Hee University, Seoul, Korea (the Republic of)

Hyun Ji Lim, MS

• Lee, Tae Hoon, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)

Tae Hoon Lee, PhD

• Moon, Young yoon, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)

Young yoon Moon

• Joo, Yoosun, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)

Yoosun Joo, MD

• Jung, Su Woong, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)

Su Woong Jung, MD, PhD

• Kim, Yang Gyun, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)

Yang Gyun Kim, MD

• Lee, Sangho, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)

Sangho Lee, DrMed

• Moon, Ju young, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)

Ju young Moon, MD, PhD

Background

Lipids play crucial roles in various biological processes and are involved in the development and progression of many diseases, including diabetes. The lipid compositions in the renal cortex and medulla are different, each performing distinct functions in maintaining body homeostasis. Increased accumulation of lipid droplets and alterations in lipid metabolism have been reported, suggesting potential implications for understanding pathological mechanisms associated with diabetes.

Methods

To further explore lipidomic variations across kidney compartments, we employed tandem mass spectrometry and MALDI-Imaging mass spectrometry. We utilized db/db mice, a widely used model for examining diabetic nephropathy, and lipid extractions were performed on the cortex and medulla for LC-MS/MS while for IMS assessment, we prepared FFPE kidney tissue slides using the whole kidney.

Results

As a result, we identified a total of 390 lipids in medulla and 396 lipids in the cortex. The lipid profile differed between the renal cortex and medulla. In the medulla, ceramide-1-phosphate showed significant changes, while in the cortex, ceramide and phosphatidic acid were notably altered. When comparing the MALDI imaging results with the LC-MS/MS results, PC 34:4 and PC 34:3 increased in the medulla, while PC 32:0 increased in the cortex. Furthermore, the levels of PA 36:0 decreased in the cortex, while TG 46:0 and PE 40:3 decreased in the medulla. Pathway enrichment analysis using relational database of metabolomics pathways (RaMP) revealed distinct biological pathway alterations between renal cortex and medulla. Notably, signaling pathways such as insulin signaling exhibited showed significant changes in the medulla, whereas inflammation and immune-related pathways were altered in the cortex.

Conclusion

Our comprehensive examination of lipid composition revealed distinct differences in lipid metabolism between the kidney cortex and medulla. This study could help in identifying pathogenic alterations in the kidney, shedding light on the mechanisms underlying lipid dysmetabolism and diabetic kidney disease.