Ceramides in Metabolism: Key Lipotoxic Players
- 10 February 2021
- journal article
- review article
- Published by Annual Reviews in Annual Review of Physiology
- Vol. 83 (1), 303-330
- https://doi.org/10.1146/annurev-physiol-031620-093815
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
This publication has 204 references indexed in Scilit:
- Plasma sphingolipids are biomarkers of metabolic syndrome in non-human primates maintained on a Western-style dietInternational Journal of Obesity, 2012
- Transcriptional Control of Adipose Lipid Handling by IRF4Cell Metabolism, 2011
- Implication of Sphingomyelin/Ceramide Molar Ratio on the Biological Activity of SphingomyelinaseBiophysical Journal, 2010
- New loci associated with kidney function and chronic kidney diseaseNature Genetics, 2010
- Antagonism of Human Adiponectin Receptors and Their Membrane Progesterone Receptor Paralogs by TNFα and a Ceramidase InhibitorBiochemistry, 2009
- The sphingolipid salvage pathway in ceramide metabolism and signalingCellular Signalling, 2008
- Selective versus Total Insulin Resistance: A Pathogenic ParadoxCell Metabolism, 2008
- Inflammation and metabolic disordersNature, 2006
- Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrationsMitochondrion, 2006
- Sphingolipids—The Enigmatic Lipid Class: Biochemistry, Physiology, and PathophysiologyToxicology and Applied Pharmacology, 1997