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Lipotoxicity contributes to endothelial dysfunction: A focus on the contribution from ceramide

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Abstract

Cardiovascular complications are the leading causes of morbidity and mortality in individuals with obesity, type 2 diabetes mellitus (T2DM), and insulin resistance. Complications include pathologies specific to large (atherosclerosis, cardiomyopathy) and small (retinopathy, nephropathy, neuropathy) vessels. Common among all of these pathologies is an altered endothelial cell phenotype i.e., endothelial dysfunction. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. Hyperglycemia, oxidative stress, activation of the renin-angiotensin system, and increased pro-inflammatory cytokines are systemic disturbances in individuals with obesity, T2DM, and insulin resistance and each of these contribute independently and synergistically to decreasing NO bioavailability. This review will examine the contribution from elevated circulating fatty acids in these subjects that lead to lipotoxicity. Particular focus will be placed on the fatty acid metabolite ceramide.

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Acknowledgments

JDS is supported by a National Institutes of Health (NIH) grant 2R15HL091493, American Diabetes Association (ADA) Research Grant 1-12-BS-208, ADA 7-08-RA-164, and the University of Utah College of Health and School of Medicine, EDA is supported by NIH grants R01 DK092065, R01HL108379, U01 HL087947, and is an established investigator of the AHA.

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  1. College of Health, University of Utah, School of Medicine, Salt Lake City, UT, USA

    J. David Symons

  2. Program in Molecular Medicine, University of Utah, School of Medicine, Salt Lake City, UT, USA

    E. Dale Abel

  3. Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, 15 N 2030 E., Bldg. #585, Rm. 168, Salt Lake City, UT, 84112, USA

    J. David Symons

  4. Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, 15 N 2030 E., Bldg. #533, Rm. 3110B, Salt Lake City, UT, 84112, USA

    E. Dale Abel

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Symons, J.D., Abel, E.D. Lipotoxicity contributes to endothelial dysfunction: A focus on the contribution from ceramide. Rev Endocr Metab Disord 14, 59–68 (2013). https://doi.org/10.1007/s11154-012-9235-3

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