Projects per year
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.
Original language | English |
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Pages (from-to) | 718 - 730 |
Number of pages | 13 |
Journal | Cell Metabolism |
Volume | 21 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2015 |
Projects
- 2 Finished
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The CDP ethanolamine pathway: a new player in obesity induced insulin resistance
Bruce, C. R. & Febbraio, M.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/11 → 31/12/14
Project: Research
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NHMRC Research Fellowship
Watt, M. (Primary Chief Investigator (PCI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/10 → 31/12/19
Project: Research