UP-REGULATION OF 5'-AMP-ACTIVATED PROTEIN-KINASE IS RESPONSIBLE FOR THE INCREASE IN MYOCARDIAL FATTY-ACID OXIDATION RATES FOLLOWING BIRTH IN THE NEWBORN RABBIT

In newborn rabbits, fatty acid oxidation rates in the heart significan tly increase between 1 and 7 days after birth. This is due in part to a decrease in malonyl coenzyme A (CoA) production by acetyl CoA carbox ylase (ACC). In other tissues, 5'-AMP-activated protein kinase (AMPK) can phosphorylate and inhibit ACC activity. In this study, we show tha t 1- and 7-day-old rabbit hearts have a high AMPK activity, with AMPK expression and activity being greatest in 7-day-old hearts. Hearts wer e also perfused in the Langendorff mode with Krebs-Henseleit buffer co ntaining 0.4 mmol/L [C-14]palmitate and 11 mmol/L glucose+/-100 mu U/m L insulin. In the absence of insulin, fatty acid oxidation rates were significantly higher in 7-day-old hearts compared with 1-day-old heart s. AMPK activity was also greater in 7-day-old hearts compared with 1- day-old hearts (909+/-60 and 585+/-75 pmol . min(-1) . mg protein(-1) respectively; P<.05). In 1-day-old hearts, the presence of insulin res ulted in a significant decrease in AMPK activity, an increase in ACC a ctivity, and a decrease in fatty acid oxidation rates. In 7-day-old he arts, AMPK activity was also decreased by insulin, although ACC activi ty remained low and fatty acid oxidation rates remained high. Stimulat ion of AMPK in 7-day-old hearts with 200 mu mol/L 5-amino 4-imidazolec arboxamide ribotide resulted in a further decrease in ACC activity and an increase in fatty acid oxidation rates. These data suggest that AM PK, ACC, and fatty acid oxidation are sensitive to insulin in 1-day-ol d rabbit hearts and that the decrease in circulating insulin levels se en after birth leads to an increased activity of AMPK. This can then l ead to a phosphorylation and inhibition of ACC activity, with a result ant increase in fatty acid oxidation rates.