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Current Diabetes Reports

, 19:144 | Cite as

Crosstalk Between Lipids and Mitochondria in Diabetic Kidney Disease

  • G. Michelle Ducasa
  • Alla Mitrofanova
  • Alessia FornoniEmail author
Microvascular Complications—Nephropathy (M Afkarian and B Roshanravan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Microvascular Complications—Nephropathy

Abstract

Purpose of Review

The goal of this review is to review the role that renal parenchymal lipid accumulation plays in contributing to diabetic kidney disease (DKD), specifically contributing to the mitochondrial dysfunction observed in glomerular renal cells in the context of DKD development and progression.

Recent Findings

Mitochondrial dysfunction has been observed in experimental and clinical DKD. Recently, Ayanga et al. demonstrate that podocyte-specific deletion of a protein involved in mitochondrial dynamics protects from DKD progression. Furthermore, our group has recently shown that ATP-binding cassette A1 (a protein involved in cholesterol and phospholipid efflux) is significantly reduced in clinical and experimental DKD and that genetic or pharmacological induction of ABCA1 is sufficient to protect from DKD. ABCA1 deficiency in podocytes leads to mitochondrial dysfunction observed with alterations of mitochondrial lipids, in particular, cardiolipin (a mitochondrial-specific phospholipid). However, through pharmacological reduction of cardiolipin peroxidation DKD progression is reverted.

Summary

Lipid metabolism is significantly altered in the diabetic kidney and renders cellular components, such as the podocyte, susceptible to injury leading to worsened DKD progression. Dysfunction of the lipid metabolism pathway can also lead to mitochondrial dysfunction and mitochondrial lipid alteration. Future research aimed at targeting mitochondrial lipids content and function could prove to be beneficial for the treatment of DKD.

Keywords

Diabetic kidney disease Podocyte Mitochondria Cardiolipin ABCA1 Lipid metabolism 

Notes

Authors’ Contributions

GMD and AM prepared a draft of the manuscript. AM focused primarily on the “Lipids in DKD” section and GMD focused primarily on the “Mitochondrial Defects and Dysfunction in DKD” section. AF reviewed and improved the entire manuscript.

Funding Information

Research in Dr. Alessia Fornoni’s laboratory is supported by the NIH grants R01DK117599, R01DK104753, R01CA227493, U54DK083912, UM1DK100846, U01DK116101, and UL1TR000460 (Miami Clinical Translational Science Institute).

Compliance with Ethical Standards

Conflict of Interest

Alessia Fornoni is an investor on pending or issued patents (US 10,183,038 and US 10,052,345) aimed at diagnosing or treating proteinuric kidney diseases. She stands to gain royalties from the future commercialization of these patents. She is Chief Scientific Officer of L&F Health LLC and is a consultant for Variant Pharmaceuticals. Variant Pharmaceuticals has licensed worldwide rights from L&F Research to develop and commercialize hydroxypropyl-beta-cyclodextrin for the treatment of kidney disease. She is the founder of LipoNexT LLC. She is also supported by Roche and Boehringer Ingelheim.

Michelle Ducasa and Alla Mitrofanova declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • G. Michelle Ducasa
    • 1
    • 2
  • Alla Mitrofanova
    • 1
    • 2
    • 3
  • Alessia Fornoni
    • 1
    • 2
    Email author
  1. 1.Katz Family Division of Nephrology and Hypertension, Department of MedicineUniversity of Miami, Miller School of MedicineMiamiUSA
  2. 2.Peggy and Harold Katz Family Drug Discovery CenterUniversity of Miami, Miller School of MedicineMiamiUSA
  3. 3.Department of SurgeryUniversity of Miami, Miller School of MedicineMiamiUSA

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