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

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posted on 05.05.2015, 00:00 authored by Ahrathy SelathuraiAhrathy Selathurai, Greg KowalskiGreg Kowalski, M L Burch, P Sepulveda, S Risis, R S Lee-Young, Severine LamonSeverine Lamon, P J Meikle, Amanda Genders, Sean McgeeSean Mcgee, M J Watt, Aaron RussellAaron Russell, M Frank, S Jackowski, M A Febbraio, Clinton BruceClinton Bruce
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.

History

Journal

Cell Metabolism

Volume

21

Issue

5

Pagination

718 - 730

Publisher

Elsevier

Location

United States

ISSN

1932-7420

eISSN

1932-7420

Language

eng

Publication classification

C Journal article; C1 Refereed article in a scholarly journal

Copyright notice

2015, Elsevier