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The Evolving Understanding of the Contribution of Lipid Metabolism to Diabetic Kidney Disease

  • Microvascular Complications—Nephropathy (T Isakova, Section Editor)
  • Published:
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Abstract

Although diabetes is mainly diagnosed based on elevated glucose levels, dyslipidemia is also observed in these patients. Chronic kidney disease (CKD), a frequent occurrence in patients with diabetes, is associated with major abnormalities in circulating lipoproteins and renal lipid metabolism. At baseline, most renal epithelial cells rely on fatty acids as their energy source. CKD, including that which occurs in diabetes, is characterized by tubule epithelial lipid accumulation. Whether this is due to increased uptake or greater local fatty acid synthesis is unknown. We have recently shown that CKD also leads to decreased fatty acid oxidation, which might be an additional mechanism leading to lipid accumulation. Defective fatty acid utilization causes energy depletion resulting in increased apoptosis and dedifferentiation, which in turn contributes to fibrosis and CKD progression. Enhanced fatty acid oxidation in the kidney induced by fenofibrate, a peroxisomal proliferator-activated receptor (PPAR)-α agonist, showed benefit in mouse models of CKD. Fenofibrate treatment also reduced albuminuria in patients with diabetes in multiple clinical trials. Taken together, these findings suggest that further understanding of lipid metabolism in diabetic kidney disease may lead to novel therapeutic approaches.

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Acknowledgments

Research in the Stadler and Susztak laboratories are supported by DiaComp Pilot and Feasibility grants (14GHSU1393, through Georgia Regents University/NIH) and the Pennington Foundation (K.St), NIH (K.Su) DK076077, DK087635 and HL45095, HL073029, and DK095684 (IJG).

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Conflict of Interest

Krisztian Stadler, Ira J. Goldberg, and Katalin Susztak 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

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Authors and Affiliations

  1. Oxidative Stress and Disease Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA

    Krisztian Stadler

  2. Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY, USA

    Ira J. Goldberg

  3. Division of Nephrology, Perelman School of Medicine, University of Pennsylvania, 405 Clinical Research Building, 415 CRB, 415 Curie Blvd, Philadelphia, PA, 19104, USA

    Katalin Susztak

Authors
  1. Krisztian Stadler
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  2. Ira J. Goldberg
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  3. Katalin Susztak
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Correspondence to Katalin Susztak.

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This article is part of the Topical Collection on Microvascular Complications—Nephropathy

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Stadler, K., Goldberg, I.J. & Susztak, K. The Evolving Understanding of the Contribution of Lipid Metabolism to Diabetic Kidney Disease. Curr Diab Rep 15, 40 (2015). https://doi.org/10.1007/s11892-015-0611-8

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  • DOI: https://doi.org/10.1007/s11892-015-0611-8

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