The CDP-Ethanolamine Pathway Regulates Skeletal Muscle Diacylglycerol Content and Mitochondrial Biogenesis without Altering Insulin Sensitivity.

Abstract

Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn), would influence muscle DG content and insulin sensitivity. Muscle PtdEtn synthesis was disrupted by deleting CTP:phosphoethanolamine cytidylyltransferase (ECT), the rate-limiting enzyme in the CDP-ethanolamine pathway, a major route for PtdEtn production. While PtdEtn was reduced in muscle-specific ECT knockout mice, intramyocellular and membrane-associated DG was markedly increased. Importantly, however, this was not associated with insulin resistance. Unexpectedly, mitochondrial biogenesis and muscle oxidative capacity were increased in muscle-specific ECT knockout mice and were accompanied by enhanced exercise performance. These findings highlight the importance of the CDP-ethanolamine pathway in regulating muscle DG content and challenge the DG-induced insulin resistance hypothesis.

• Authors: Ahrathy Selathurai, Greg M Kowalski, Micah L Burch, Patricio Sepulveda, Steve Risis, Robert S Lee-Young, Severine Lamon, Peter J Meikle, Amanda J Genders, Sean L McGee, Matthew J Watt, Aaron P Russell, Matthew Frank, Suzanne Jackowski, Mark A Febbraio, Clinton R Bruce
• Journal: Cell metabolism (Cell Metab) Vol. 21 Issue 5 Pg. 718-30 (May 05 2015) ISSN: 1932-7420 [Electronic] United States
• PMID: 25955207 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• 1,2-diacylglycerol
• Diglycerides
• Ethanolamines
• CDP ethanolamine
• Cytidine Diphosphate
• RNA Nucleotidyltransferases
• Ethanolamine-phosphate cytidylyltransferase
• Glucose

Topics

• Animals
• Cytidine Diphosphate (analogs & derivatives, metabolism)
• Diglycerides (metabolism)
• Ethanolamines (metabolism)
• Glucose (metabolism)
• Insulin Resistance
• Lipid Metabolism
• Mice
• Mice, Knockout
• Muscle, Skeletal (metabolism)
• Obesity (genetics, metabolism)
• Organelle Biogenesis
• RNA Nucleotidyltransferases (genetics, metabolism)