Effects of insulin-like growth factor-I on the maturation of metabolism in neonatal rat cardiomyocytes.

Myocardial metabolism shifts during the perinatal period from predominant utilization of glucose towards oxidation of fatty acids. Expression of enzymes of the fatty acid oxidation (FAO) pathway is under the control of the nuclear receptor/transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Insulin-like Growth Factor-I (IGF-I) plays an important role in the post-natal growth and differentiation of the heart. We determined the influence of IGF-I on the maturation of myocardial metabolism. In neonatal rat cardiac myocytes, expression of the FAO enzymes MCAD and M-CPT I was induced by treatment with the specific PPARalpha agonist WY-14643. Concomitant treatment with IGF-I enhanced the expression of both FAO enzymes. By comparison, treatment with FGF-2, which is required for myocyte differentiation of cardiac precursors, did not increase WY-14643-induced expression of FAO enzymes. Despite stimulation of FAO enzyme expression, IGF-I did not further enhance WY-14643-stimulated palmitate oxidation. In contrast, IGF-I relieved WY-14643-mediated inhibition of glucose uptake and promoted storage of fatty acids into cellular neutral lipids. In conclusion, IGF-I promotes a more mature pattern of FAO gene expression but, because of insulin-like metabolic effects, does not concomitantly enhance oxidation of fatty acids.