J Lipid Atheroscler.  2020 Jan;9(1):50-65. 10.12997/jla.2020.9.1.50.

Ceramides: Nutrient Signals that Drive Hepatosteatosis

Affiliations
  • 1Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA. scott.a.summers@health.utah.edu

Abstract

Ceramides are minor components of the hepatic lipidome that have major effects on liver function. These products of lipid and protein metabolism accumulate when the energy needs of the hepatocyte have been met and its storage capacity is full, such that free fatty acids start to couple to the sphingoid backbone rather than the glycerol moiety that is the scaffold for glycerolipids (e.g., triglycerides) or the carnitine moiety that shunts them into mitochondria. As ceramides accrue, they initiate actions that protect cells from acute increases in detergent-like fatty acids; for example, they alter cellular substrate preference from glucose to lipids and they enhance triglyceride storage. When prolonged, these ceramide actions cause insulin resistance and hepatic steatosis, 2 of the underlying drivers of cardiometabolic diseases. Herein the author discusses the mechanisms linking ceramides to the development of insulin resistance, hepatosteatosis and resultant cardiometabolic disorders.

Keyword

Ceramides; Steatohepatitis; Insulin resistance; Non-alcoholic fatty liver disease; Diabetes

MeSH Terms

Carnitine
Ceramides*
Fatty Acids
Fatty Acids, Nonesterified
Fatty Liver
Glucose
Glycerol
Hepatocytes
Insulin Resistance
Liver
Metabolism
Mitochondria
Non-alcoholic Fatty Liver Disease
Triglycerides
Carnitine
Ceramides
Fatty Acids
Fatty Acids, Nonesterified
Glucose
Glycerol
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