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Am J Physiol Endocrinol Metab 279: E259-E265, 2000;
0193-1849/00 $5.00
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Vol. 279, Issue 2, E259-E265, August 2000

Malonyl-CoA content and fatty acid oxidation in rat muscle and liver in vivo

David Chien1, David Dean1, Asish K. Saha1, J. P. Flatt2, and Neil B. Ruderman1

1 Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston Medical Center, Boston 02118; and 2 Department of Biochemistry and Molecular Biology, University of Massachusetts, Worcester, Massachusetts 01655

Malonyl-CoA acutely regulates fatty acid oxidation in liver in vivo by inhibiting carnitine palmitoyltransferase. Thus rapid increases in the concentration of malonyl-CoA, accompanied by decreases in long-chain fatty acyl carnitine (LCFA-carnitine) and fatty acid oxidation have been observed in liver of fasted-refed rats. It is less clear that it plays a similar role in skeletal muscle. To examine this question, whole body respiratory quotients (RQ) and the concentrations of malonyl-CoA and LCFA-carnitine in muscle were determined in 48-h-starved rats before and at various times after refeeding. RQ values were 0.82 at baseline and increased to 0.93, 1.0, 1.05, and 1.09 after 1, 3, 12, and 18 h of refeeding, respectively, suggesting inhibition of fat oxidation in all tissues. The increases in RQ at each time point correlated closely (r = 0.98) with increases (50-250%) in the concentration of malonyl-CoA in soleus and gastrocnemius muscles and decreases in plasma FFA and muscle LCFA-carnitine levels. Similar changes in malonyl-CoA and LCFA-carnitine were observed in liver. The increases in malonyl-CoA in muscle during refeeding were not associated with increases in the assayable activity of acetyl-CoA carboxylase (ACC) or decreases in the activity of malonyl-CoA decarboxylase (MCD). The results suggest that, during refeeding after a fast, decreases in fatty acid oxidation occur rapidly in muscle and are attributable both to decreases in plasma FFA and increases in the concentration of malonyl-CoA. They also suggest that the increase in malonyl-CoA in this situation is not due to changes in the assayable activity of either ACC or MCD or an increase in the cytosolic concentration of citrate.

acetyl-CoA carboxylase; insulin; glucose; long-chain fatty acyl carnitine; starvation; refeeding


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