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Rev Endocr Metab Disord. 2013 Mar;14(1):59-68. doi: 10.1007/s11154-012-9235-3.

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

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1
College of Health, University of Utah, School of Medicine, Salt Lake City, UT, USA. j.david.symons@hsc.utah.edu

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.

PMID:
23292334
PMCID:
PMC4180664
DOI:
10.1007/s11154-012-9235-3
[Indexed for MEDLINE]
Free PMC Article
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