Ontogeny of mRNA expression and activity of long-chain acyl-CoA synthetase (ACSL) isoforms in Mus musculus heart.
Long-chain acyl-CoA synthetases (ACSL) activate fatty acids (FA) and provide substrates for virtually every metabolic pathway that catabolizes FA or synthesizes complex lipids. We have hypothesized that each of the five cloned ACSL isoforms partitions FA towards specific downstream pathways. Adult heart expresses all five cloned ACSL isoforms, but their independent functional roles have not been elucidated. Studies implicate ACSL1 in both oxidative and lipid synthetic pathways. To clarify the functional role of ACSL1 and the other ACSL isoforms (3-6), we examined ACS specific activity and Acsl mRNA expression in the developing mouse heart which increases FA oxidative pathways for energy production after birth. Compared to the embryonic heart, ACS specific activity was 14-fold higher on post-natal day 1 (P1). On P1, as compared to the fetus, only Acsl1 mRNA increased, whereas transcripts for the other Acsl isoforms remained the same, suggesting that ACSL1 is the major isoform responsible for activating long-chain FA for myocardial oxidation after birth. In contrast, the mRNA abundance of Acsl3 was highest on E16, and decreased dramatically by P7, suggesting that ACSL3 may play a critical role during the development of the fetal heart. Our data support the hypothesis that each ACSL has a specific role in the channeling of FA towards distinct metabolic fates.
de Jong
Hendrik
H
Department of Nutrition, University of North Carolina at Chapel Hill, CB# 7461, NC 27599, USA.
Neal
Andrea C
AC
Coleman
Rosalind A
RA
Lewin
Tal M
TM
D000818:Animals; D000831:Animals, Newborn; D003066:Coenzyme A Ligases / Q000096:biosynthesis* / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005333:Fetus / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006321:Heart / Q000254:growth & development; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D050356:Lipid Metabolism; D051379:Mice; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D005227:Fatty Acids; D007527:Isoenzymes; D012333:RNA, Messenger; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase