ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO496

Impairment of CPT-1α and Fatty Acid Metabolism Aggravates Renal Fibrosis During Aging

Session Information

  • CKD: Mechanisms - I
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Yuan, Qi, Nanjing Medical University, Jiangsu Nanjing, China
  • Zhou, Yang, Second Affiliated Hospital, Nanjing Medical University, Nanjing, JIangSu, China
  • Yang, Junwei, Second Affiliated Hospital, Nanjing Medical University, Nanjing, JIangSu, China
Background

Defects in renal fatty acid metabolism (FAM) pathway have been implicated in the development of renal fibrosis. Aged kidneys show significantly increased fibrosis with impaired kidney function. The mechanisms underlying the effects of FAM on renal aging and fibrosis have not been investigated. In this study, we investigated carnitine palmitoyltransferase-1α (CPT-1α) and FAM pathway as regulators of age-associated renal fibrosis.

Methods

Renal biopsy samples from 126 patients were examined by masson trichrome staining, oil red O staining and immunohistochemical staining for CPT-1α. To evaluate the effects of CPT-1α deficiency on age-associated renal fibrosis, age-matched tubular cell specific CPT-1α-/- mice and their wild-type littermates were used.

Results

In patients, fibrosis and lipid accumulation in tubulointerstitial spaces were associated with the age of patients. After been followed up for 5 years, age and lipid accumulation were risk factors for the progression of renal fibrosis. As compared with wild-type litermates, renal dysfunction measure by blood urine nitrogen and serum creatinine, tubular damage evaluated by urinary KIM-1, NGAL and NAG, urinary albumin and protein excretion were all more severe in mice with tubular specific deficiency of CPT-1α at the age of 1-year-old. Meanwhile, more lipid accumulation, tubulointerstitial fibrosis, extracellular matrix deposition were observed in CPT-1α-/- mice at the age of 1-year-old. The increased expression of aging proteins (p21, p53, PCNA), inflammatory factors (NF-κB, CD3, IL-1, IL-18) and apoptosis molecule (cleaved caspase3) and decreased expression of autophagy (Atg12, Beclin-1, LC3β, p62) in kidney of CPT-1α-/- mice were accompanied by the dysregulated expression of FAM proteins, including PPARα, CD36, ACADL, ACOX1, FASN and ACLY. In primarily cultured tubular cells, down-regulation of CPT-1α resulted in increased ROS and decreased mitochondrial energy production.

Conclusion

Impairment of CPT-1α and fatty acid metabolism in tubular cells aggravates renal aging and fibrosis.

Funding

  • Government Support - Non-U.S.