Decreased hepatic fatty acid oxidation at weaning in the rat is not linked to a variation of malonyl-CoA concentration.
In rats weaned on a high-carbohydrate diet, hepatic fatty acid oxidation capacity is decreased when compared to suckling rats. Previous studies (Benito et al., 1979) suggested that a malonyl-CoA-dependent mechanism could be at the origin of this decrease. Studies on isolated hepatocytes show that despite, respectively, a low and a high lipogenic rate in suckling and weaned rats, malonyl-CoA concentrations are similar in the two groups. This might be due to the lower ratio fatty acid synthetase/acetyl-CoA carboxylase (EC 6.4.1.2) activities during suckling than after weaning. Different rates of hepatic fatty acid oxidation despite similar malonyl-CoA concentrations can be explained by the 2.5-fold higher carnitine palmitoyltransferase I (EC 2.3.1.21) activity in suckling rats together with a 7-fold higher Ki for malonyl-CoA. This precludes a tight control of fatty acid oxidation by [malonyl-CoA] in suckling rats. Weaning on a high-fat carbohydrate-free diet abolishes the changes previously described for the kinetic characteristics of carnitine palmitoyltransferase I suggesting that nutritional modifications rather than a developmental stage are involved. Thus, during the suckling-weaning transition, a variation of [malonyl-CoA] is not responsible for the decrease in hepatic fatty acid oxidation. It involves, in addition, a decrease in carnitine palmitoyltransferase I activity and an increase of the sensitivity of this enzyme to malonyl-CoA.
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D014886:Weaning
D000214:Acyl Coenzyme A; D004040:Dietary Carbohydrates; D005227:Fatty Acids; D008055:Lipids; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D001275:ATP Citrate (pro-S)-Lyase; D000103:Acetyl-CoA Carboxylase