IMPACT OF PROTEIN RESTRICTION ON THE REGULATION OF CARDIAC CARNITINE PALMITOYLTRANSFERASE BY MALONYL-COA

Using a rat model of isocaloric protein restriction (8 v 20% protein d iet), the study tested the hypothesis that growth retardation in utero , induced by maternal protein malnutrition, influences cardiac carniti ne pal mitoyltransferase (CPT) activity and regulation by malonyl-CoA in the newborn period, as well as in the offspring's adult life. The s usceptibility of cardiac CPT to inhibition by malonyl-CoA was greater in adulthood than in hearts of 4-day-old neonatal rats, consistent wit h decreased expression of the L-CPT I isoform and increased expression of the M-CPT I isoform in adulthood. Maternal protein restriction dur ing pregnancy resulted in reduced foetal growth and significantly (P<0 .05) lower rates of cardiac glucose utilization in vivo in the adult o ffspring, suggesting a switch to the use of substrates other than gluc ose. Maternal protein restriction did not affect CPT activity in heart s of 4-day-old neonatal offspring and, Furthermore, the relative sensi tivity of CPT activity to malonyl-CoA inhibition was unchanged by mate rnal protein restriction. It is therefore unlikely that maternal prote in malnutrition has ally major impact on cardiac mitochondrial fatty a cid oxidation in the offspring during early postnatal development thro ugh altered regulatory characteristics of CPT. Transfer of rats previo usly maintained on 8% protein diet to 20% protein diet at weaning did not influence age-dependent changes in cardiac CPT activity or increas e the susceptibility of cardiac CPT to inhibition by malonyl-CoA. Card iac CPT activities and the susceptibility of cardiac CPT activities to malonyl-CoA inhibition in adulthood did not differ significantly betw een rats maintained on 8 or 20% protein throughout. Palmitate oxidatio n was suppressed to a similar extent by glucose in cardiac myocytes fr om adult rats maintained on 20% protein diet or 8% protein diet throug hout and from rats transferred from 8 to 20% protein diet at weaning, The results exclude cardiac CPT activity as a direct target for the me tabolic programming of cardiac function and cardiovascular disease ass ociated with early growth retardation. (C) 1998 Academic Press.