RRC ID 65720
Author Valentine WJ, Tokuoka SM, Hishikawa D, Kita Y, Shindou H, Shimizu T.
Title LPAAT3 incorporates docosahexaenoic acid into skeletal muscle cell membranes and is upregulated by PPARδ activation.
Journal J Lipid Res
Abstract Adaption of skeletal muscle to endurance exercise includes PPARδ- and AMP-activated protein kinase (AMPK)/PPARγ coactivator 1α-mediated transcriptional responses that result in increased oxidative capacity and conversion of glycolytic to more oxidative fiber types. These changes are associated with whole-body metabolic alterations including improved glucose handling and resistance to obesity. Increased DHA (22:6n-3) content in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is also reported in endurance exercise-trained glycolytic muscle; however, the DHA-metabolizing enzymes involved and the biological significance of the enhanced DHA content are unknown. In the present study, we identified lysophosphatidic acid acyltransferase (LPAAT)3 as an enzyme that was upregulated in myoblasts during in vitro differentiation and selectively incorporated DHA into PC and PE. LPAAT3 expression was increased by pharmacological activators of PPARδ or AMPK, and combination treatment led to further increased LPAAT3 expression and enhanced incorporation of DHA into PC and PE. Our results indicate that LPAAT3 was upregulated by exercise-induced signaling pathways and suggest that LPAAT3 may also contribute to the enhanced phospholipid-DHA content of endurance-trained muscles. Identification of DHA-metabolizing enzymes in the skeletal muscle will help to elucidate broad metabolic effects of DHA.
Volume 59(2)
Pages 184-194
Published 2018-2-1
DOI 10.1194/jlr.M077321
PII S0022-2275(20)34224-3
PMID 29284664
PMC PMC5794415
MeSH Acyltransferases / metabolism* Animals Cell Membrane / drug effects* Cell Membrane / metabolism Cells, Cultured Docosahexaenoic Acids / pharmacology* Mice Muscle, Skeletal / drug effects* Muscle, Skeletal / metabolism PPAR delta / metabolism* Up-Regulation / drug effects
IF 4.483
Human and Animal Cells C2C12(RCB0987)