Format

Send to

Choose Destination
Trends Pharmacol Sci. 2017 Jul;38(7):649-665. doi: 10.1016/j.tips.2017.04.004. Epub 2017 May 24.

Roles of Diacylglycerols and Ceramides in Hepatic Insulin Resistance.

Author information

1
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: gerald.shulman@yale.edu.

Abstract

Although ample evidence links hepatic lipid accumulation with hepatic insulin resistance, the mechanistic basis of this association is incompletely understood and controversial. Diacylglycerols (DAGs) and ceramides have emerged as the two best-studied putative mediators of lipid-induced hepatic insulin resistance. Both lipids were first associated with insulin resistance in skeletal muscle and were subsequently hypothesized to mediate insulin resistance in the liver. However, the putative roles for DAGs and ceramides in hepatic insulin resistance have proved more complex than originally imagined, with various genetic and pharmacologic manipulations yielding a vast and occasionally contradictory trove of data to sort. In this review we examine the state of this field, turning a critical eye toward both DAGs and ceramides as putative mediators of lipid-induced hepatic insulin resistance.

KEYWORDS:

ceramide; ectopic lipid; insulin receptor kinase; insulin resistance; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; protein kinase C epsilon

PMID:
28551355
PMCID:
PMC5499157
DOI:
10.1016/j.tips.2017.04.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center