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

  • J. David SymonsEmail author
  • E. Dale Abel


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.


Pathways and mechanisms Vascular dysfunction Ceramide Adiponectin Nitric oxide Reactive oxygen species Insulin resistance Obesity Inflammation Mitochondria Endothelial dysfunction Glucotoxicity Diabetes 



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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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.College of HealthUniversity of Utah, School of MedicineSalt Lake CityUSA
  2. 2.Program in Molecular MedicineUniversity of Utah, School of MedicineSalt Lake CityUSA
  3. 3.Division of Endocrinology, Metabolism, and DiabetesUniversity of Utah, School of MedicineSalt Lake CityUSA
  4. 4.Division of Endocrinology, Metabolism, and DiabetesUniversity of Utah, School of MedicineSalt Lake CityUSA

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