Abstract: SA-PO523
The Role of ABCA1 on the Glomerular Lipid Accumulation and Renal Injury in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Park, Jimin, Yonsei University, Seoul, Korea (the Republic of)
- Kim, Seonghun, Yonsei University, Seoul, Korea (the Republic of)
- Nam, Boyoung, Yonsei University, Seoul, Korea (the Republic of)
- Yoo, Tae-Hyun, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
Background
Glomerular lipid accumulation is one of the pathologic characteristics of diabetic kidney disease (DKD). Recent evidences suggested that ATP-binding cassette transporters A1 (ABCA1) has a particular effect on the cellular lipid homeostasis. We aimed to evaluate the role of ABCA1 on the lipid accumulation in glomeruli and podocyte under the diabetic conditions.
Methods
In vitro, mouse podocytes were stimulated with high glucose (HG) and palmitic acid (PA), and treated an GW683965, agonist of ABCA1. In vivo, C57BL/6 and ABCA1 knockout (KO) mice were maintained with high fat diet for 12 weeks with low dose streptozocin intraperitoneal injection. GW683965 was administered via osmotic pump in db/m or db/db mice. Urinary albumin-to-creatinine ratio (ACR), total cholesterol and triglyceride in kidney tissues were measured. RhoA activity and BODIPY 493/503 staining were performed in the kidney. Foot process effacement in glomeruli was evaluated by transmission electron microscopy. Apoptosis, mitochondrial morphology and energy metabolic key enzymes were evaluated both in vitro and vivo.
Results
Blood glucose, ACR, serum cholesterol and triglyceride were significantly increased and foot process effacement was prominent in diabetic mice. These changes were exaggerated in the ABCA1 KO mouse with diabetes, whereas abrogated by GW683965 treatment. Renal cholesterol and triglyceride contents were higher in ABCA1 KO mice with diabetes or lower in GW683965 treated mice than those in control and diabetic mice. Mitochondrial morphology and the expression of energy metabolic enzymes were changed in the kidneys of diabetic ABCA1 KO mice or GW683965 treated mice. In vitro, the intracellular lipid contents were increased and apoptosis combined with mitochondrial swelling and crista disruption were also increased in podocytes with HG and PA stimuli. All of these changes were ameliorated through GW683965 treatment.
Conclusion
These findings suggest that ABCA1 plays an important role in the glomerular lipid accumulation and renal injury under diabetic conditions and that ABCA1 can be a promising therapeutic target in patients with DKD.