Affiliation:
1. Department of Internal Medicine, Division of Endocrinology, Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA;
2. Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah 84112, USA;
Abstract
The global prevalence of metabolic diseases such as type 2 diabetes mellitus, steatohepatitis, myocardial infarction, and stroke has increased dramatically over the past two decades. These obesity-fueled disorders result, in part, from the aberrant accumulation of harmful lipid metabolites in tissues not suited for lipid storage (e.g., the liver, vasculature, heart, and pancreatic beta-cells). Among the numerous lipid subtypes that accumulate, sphingolipids such as ceramides are particularly impactful, as they elicit the selective insulin resistance, dyslipidemia, and ultimately cell death that underlie nearly all metabolic disorders. This review summarizes recent findings on the regulatory pathways controlling ceramide production, the molecular mechanisms linking the lipids to these discrete pathogenic events, and exciting attempts to develop therapeutics to reduce ceramide levels to combat metabolic disease.
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110 articles.
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