Ceramides in Metabolism: Key Lipotoxic Players

Annu Rev Physiol. 2021 Feb 10:83:303-330. doi: 10.1146/annurev-physiol-031620-093815. Epub 2020 Nov 6.

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.

Keywords: atherosclerosis; ceramides; diabetes; dyslipidemia; insulin resistance; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Ceramides / metabolism*
  • Humans
  • Insulin Resistance / physiology
  • Lipid Metabolism / physiology*
  • Metabolic Diseases / metabolism
  • Sphingolipids / metabolism

Substances

  • Ceramides
  • Sphingolipids