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

Selathurai,A, Kowalski,GM, Burch,ML, Sepulveda,P, Risis,S, Lee-Young,RS, Lamon,S, Meikle,PJ, Genders,AJ, McGee,SL, Watt,MJ, Russell,AP, Frank,M, Jackowski,S, Febbraio,MA and Bruce,CR 2015, The CDP-Ethanolamine Pathway Regulates Skeletal Muscle Diacylglycerol Content and Mitochondrial Biogenesis without Altering Insulin Sensitivity., Cell metabolism, vol. 21, no. 5, pp. 718-730, doi: 10.1016/j.cmet.2015.04.001.

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Title The CDP-Ethanolamine Pathway Regulates Skeletal Muscle Diacylglycerol Content and Mitochondrial Biogenesis without Altering Insulin Sensitivity.
Author(s) Selathurai,A
Kowalski,GM
Burch,ML
Sepulveda,P
Risis,S
Lee-Young,RS
Lamon,SORCID iD for Lamon,S orcid.org/0000-0002-3271-6551
Meikle,PJ
Genders,AJ
McGee,SL
Watt,MJ
Russell,AP
Frank,M
Jackowski,S
Febbraio,MA
Bruce,CRORCID iD for Bruce,CR orcid.org/0000-0002-0515-3343
Journal name Cell metabolism
Volume number 21
Issue number 5
Start page 718
End page 730
Publisher Elsevier
Place of publication United States
Publication date 2015-05
ISSN 1932-7420
Summary 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.
Language eng
DOI 10.1016/j.cmet.2015.04.001
Field of Research 111603 Systems Physiology
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30073281

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
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Created: Tue, 26 May 2015, 15:39:02 EST

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