Holness M J, Priestman D A, Sugden M C
Department of Biochemistry, Faculty of Basic Medical Sciences, St Bartholomew's, UK.
J Mol Cell Cardiol. 1998 Jul;30(7):1381-90. doi: 10.1006/jmcc.1998.0709.
Using a rat model of isocaloric protein restriction (8 v 20% protein diet), the study tested the hypothesis that growth retardation in utero, induced by maternal protein malnutrition, influences cardiac carnitine palmitoyltransferase (CPT) activity and regulation by malonyl-CoA in the newborn period, as well as in the offspring's adult life. The susceptibility of cardiac CPT to inhibition by malonyl-CoA was greater in adulthood than in hearts of 4-day-old neonatal rats, consistent with decreased expression of the L-CPT I isoform and increased expression of the M-CPT I isoform in adulthood. Maternal protein restriction during pregnancy resulted in reduced foetal growth and significantly (P < 0.05) lower rates of cardiac glucose utilization in vivo in the adult offspring, suggesting a switch to the use of substrates other than glucose. Maternal protein restriction did not affect CPT activity in hearts of 4-day-old neonatal offspring and, furthermore, the relative sensitivity of CPT activity to malonyl-CoA inhibition was unchanged by maternal protein restriction. It is therefore unlikely that maternal protein malnutrition has any major impact on cardiac mitochondrial fatty acid oxidation in the offspring during early postnatal development through altered regulatory characteristics of CPT. Transfer of rats previously maintained on 8% protein diet to 20% protein diet at weaning did not influence age-dependent changes in cardiac CPT activity or increase the susceptibility of cardiac CPT to inhibition by malonyl-CoA. Cardiac CPT activities and the susceptibility of cardiac CPT activities to malonyl-CoA inhibition in adulthood did not differ significantly between rats maintained on 8 or 20% protein throughout. Palmitate oxidation was suppressed to a similar extent by glucose in cardiac myocytes from adult rats maintained on 20% protein diet or 8% protein diet throughout and from rats transferred from 8 to 20% protein diet at weaning. The results exclude cardiac CPT activity as a direct target for the metabolic programming of cardiac function and cardiovascular disease associated with early growth retardation.
利用等热量蛋白质限制的大鼠模型（8%对20%蛋白质饮食），该研究检验了以下假设：母体蛋白质营养不良所致的子宫内生长迟缓会影响新生儿期以及子代成年期心脏肉碱棕榈酰转移酶（CPT）的活性及丙二酰辅酶A对其的调节。成年期心脏CPT对丙二酰辅酶A抑制作用的敏感性高于4日龄新生大鼠的心脏，这与成年期L-CPT I亚型表达降低和M-CPT I亚型表达增加一致。孕期母体蛋白质限制导致胎儿生长受限，成年子代心脏在体内的葡萄糖利用率显著降低（P<0.05），提示转向使用除葡萄糖以外的底物。母体蛋白质限制不影响4日龄新生子代心脏的CPT活性，此外，母体蛋白质限制并未改变CPT活性对丙二酰辅酶A抑制作用的相对敏感性。因此，母体蛋白质营养不良不太可能通过改变CPT的调节特性对产后早期子代心脏线粒体脂肪酸氧化产生重大影响。断奶时将先前维持在8%蛋白质饮食的大鼠转移至20%蛋白质饮食，并不影响心脏CPT活性的年龄依赖性变化，也不会增加心脏CPT对丙二酰辅酶A抑制作用的敏感性。在整个实验过程中，维持在8%或20%蛋白质饮食的大鼠，成年期心脏CPT活性及其对丙二酰辅酶A抑制作用的敏感性并无显著差异。在整个实验过程中维持在20%蛋白质饮食的成年大鼠、维持在8%蛋白质饮食的成年大鼠以及断奶时从8%蛋白质饮食转移至20%蛋白质饮食的大鼠的心肌细胞中，葡萄糖对棕榈酸氧化的抑制程度相似。这些结果排除了心脏CPT活性是与早期生长迟缓相关的心脏功能代谢编程和心血管疾病的直接靶点。
