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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

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Rotten to the Cortex: Ceramide-Mediated Lipotoxicity in Diabetic Kidney Disease

Rebekah J Nicholson1,2, Marcus G Pezzolesi2,3, Scott A Summers1,2

  • 1Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, United States.

Frontiers in Endocrinology
|February 15, 2021
PubMed

Insights

Bioactive ceramides contribute to diabetic kidney disease (DKD) progression. Lowering ceramide levels in rodent models improved kidney function and pathology, suggesting ceramide as a therapeutic target for DKD.

Area of Science:

  • Nephrology
  • Endocrinology
  • Lipid Metabolism

Background:

  • Diabetic kidney disease (DKD) is a major complication of diabetes mellitus, leading to renal failure.
  • Current understanding of DKD pathogenesis, including renal steatosis, fibrosis, and microvascular dysfunction, is incomplete.
  • Effective DKD therapeutics are limited by this incomplete understanding.

Purpose of the Study:

  • To review the literature on the role of bioactive ceramides in DKD.
  • To explore the potential of ceramide-lowering interventions as a therapeutic strategy for DKD.

Main Methods:

  • Literature review of studies investigating ceramides in DKD.
  • Analysis of data from rodent models of DKD with ceramide manipulation.
  • Examination of human studies on sphingolipid profiles in DKD patients.

Main Results:

  • Elevated renal ceramides are observed in rodent models of DKD.
  • Genetic and pharmacological ceramide reduction improved kidney function and histopathology in rodents.
  • Distinct circulating sphingolipid profiles differentiate DKD patients from diabetic controls.

Conclusions:

  • Bioactive ceramides play a significant role in inducing local and systemic DKD pathology.
  • Ceramide-lowering interventions show promise in ameliorating DKD.
  • Ceramide represents a therapeutically tractable central lipid mediator for DKD.
Keywords:
ceramidediabetic kidney diseasediabetic nephropathylipid metabolismlipotoxicitysphingolipids

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