Malonyl-CoA acutely regulates fatty acid oxidation in liver in vivo by inhi
biting carnitine palmitoyltransferase. Thus rapid increases in the concentr
ation of malonyl-CoA, accompanied by decreases in long-chain fatty acyl car
nitine (LCFA-carnitine) and fatty acid oxidation have been observed in live
r of fasted-refed rats. It is less clear that it plays a similar role in sk
eletal 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 refeedin
g. 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 inhibiti
on 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 L
CFA-carnitine were observed in liver. The increases in malonyl-CoA in muscl
e during refeeding were not associated with increases in the assayable acti
vity of acetyl-CoA carboxylase (ACC) or decreases in the activity of malony
l-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 concentra
tion 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 AC
C or MCD or an increase in the cytosolic concentration of citrate.