Malonyl-CoA content and fatty acid oxidation in rat muscle and liver in vivo.
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.
Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston Medical Center, Boston, Massachusetts 02118, USA.
D
D
Chien
D
D
Dean
A K
AK
Saha
J P
JP
Flatt
N B
NB
Ruderman
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002262:Carboxy-Lyases / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D019343:Citric Acid / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005508:Food Deprivation / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D011659:Pulmonary Gas Exchange / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019343:Citric Acid; D008316:Malonyl Coenzyme A; D006003:Glycogen; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D000103:Acetyl-CoA Carboxylase; D002331:Carnitine