Ceramide is a cardiotoxin in lipotoxic cardiomyopathy.
Authors Park TS, Hu Y, Noh HL, Drosatos K, Okajima K, Buchanan J, Tuinei J, Homma S,
Jiang XC, Abel ED, Goldberg IJ
Submitted By Ira Goldberg on 3/4/2015
Status Published
Journal Journal of lipid research
Year 2008
Date Published 10/1/2008
Volume : Pages 49 : 2101 - 2112
PubMed Reference 18515784
Abstract Ceramide is among a number of potential lipotoxic molecules that are thought to
modulate cellular energy metabolism. The heart is one of the tissues thought to
become dysfunctional due to excess lipid accumulation. Dilated lipotoxic
cardiomyopathy, thought to be the result of diabetes and severe obesity, has
been modeled in several genetically altered mice, including animals with
cardiac-specific overexpression of glycosylphosphatidylinositol (GPI)-anchored
human lipoprotein lipase (LpL(GPI)). To test whether excess ceramide was
implicated in cardiac lipotoxicity, de novo ceramide biosynthesis was inhibited
pharmacologically by myriocin and genetically by heterozygous deletion of LCB1,
a subunit of serine palmitoyltransferase (SPT). Inhibition of SPT, a
rate-limiting enzyme in ceramide biosynthesis, reduced fatty acid and increased
glucose oxidation in isolated perfused LpL(GPI) hearts, improved systolic
function, and prolonged survival rates. Our results suggest a critical role for
ceramide accumulation in the pathogenesis of lipotoxic cardiomyopathy.

Investigators with authorship
E. Dale AbelUniversity of Iowa
Ira GoldbergNew York University School of Medicine