Ceramides in Metabolism: Key Lipotoxic Players.
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.
['Chaurasia|Bhagirath|B|', 'Summers|Scott A|SA|']
D000818:Animals D002518:Ceramides D006801:Humans D007333:Insulin Resistance D050356:Lipid Metabolism D008659:Metabolic Diseases D013107:Sphingolipids
ceramides diabetes insulin resistance dyslipidemia atherosclerosis obesity