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

Article

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.

Keywords

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

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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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