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Cell Metab. 2015 May 5;21(5):718-30. doi: 10.1016/j.cmet.2015.04.001.

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

Author information

1
Centre for Physical Activity and Nutrition (C-PAN) Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, 3125 VIC, Australia.
2
Department of Physiology, Monash University, Clayton, 3800 VIC, Australia.
3
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Prahran, 3004 VIC, Australia.
4
Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Prahran, 3004 VIC, Australia.
5
Metabolic Research Unit, Deakin University, Waurn Ponds, 3216 VIC, Australia.
6
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
7
Centre for Physical Activity and Nutrition (C-PAN) Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, 3125 VIC, Australia. Electronic address: clinton.bruce@deakin.edu.au.

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.

PMID:
25955207
DOI:
10.1016/j.cmet.2015.04.001
[Indexed for MEDLINE]
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