| First Author | Bradley RM | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids | Volume | 1863 |
| Issue | 7 | Pages | 700-711 |
| PubMed ID | 29627383 | Mgi Jnum | J:266655 |
| Mgi Id | MGI:6199872 | Doi | 10.1016/j.bbalip.2018.04.001 |
| Citation | Bradley RM, et al. (2018) Lpaatdelta/Agpat4 deficiency impairs maximal force contractility in soleus and alters fibre type in extensor digitorum longus muscle. Biochim Biophys Acta Mol Cell Biol Lipids 1863(7):700-711 |
| abstractText | Lysophosphatidic acid acyltransferase (LPAAT) delta/acylglycerophosphate acyltransferase 4 is a mitochondrial enzyme and one of five homologues that catalyze the acyl-CoA-dependent synthesis of phosphatidic acid (PA) from lysophosphatidic acid. We studied skeletal muscle LPAATdelta and found highest levels in soleus, a red oxidative fibre-type that is rich in mitochondria, and lower levels in extensor digitorum longus (EDL) (white glycolytic) and gastrocnemius (mixed fibre-type). Using Lpaatdelta-deficient mice, we found no change in soleus or EDL mass, or in treadmill time-to-exhaustion compared to wildtype littermates. There was, however, a significant reduction in the proportion of type I and type IIA fibres in EDL but, surprisingly, not soleus, where these fibre-types predominate. Also unexpectedly, there was no impairment in force generation by EDL, but a significant reduction by soleus. Oxidative phosphorylation and activity of complexes I, I+II, III, and IV in soleus mitochondria was unchanged and therefore could not explain this effect. However, pyruvate dehydrogenase activity was significantly reduced in Lpaatdelta(-/-) soleus and EDL. Analysis of cellular lipids indicated no difference in soleus triacylglycerol, but specific elevations in soleus PA and phosphatidylethanolamine levels, likely due to a compensatory upregulation of Lpaatbeta and Lpaatepsilon in Lpaatdelta(-/-) mice. An anabolic effect for PA as an activator of skeletal muscle mTOR has been reported, but we found no change in serine 2448 phosphorylation, indicating reduced soleus force generation is unlikely due to the loss of mTOR activation by a specific pool of LPAATdelta-derived PA. Our results identify an important role for LPAATdelta in soleus and EDL. |
