Robles-Valdes C, McGarry J D, Foster D W
J Biol Chem. 1976 Oct 10;251(19):6007-12.
The concentration of ketone bodies in plasma and of carnitine in various maternal, fetal, and neonatal tissues was examined during the developmental period in rats. Plasma ketone levels were low in the fetus, increased 10-fold during the first 24 h postpartom, and thereafter gradually declined such that normal values were found at the end of the suckling period. An almost identical profile was observed for liver carnitine concentrations in the baby rats. The converse was true for heart tissue, the carnitine content of which was low at birth and steadily increased to adult levels with the time of suckling. The primary source of carnitine in neonatal tissues, at least during the first 2 to 3 days postpartum, was shown to be the mother rat whose liver and milk carnitine content was very high at this time and fell as nursing continued. Experiments in which the fate of [14C]butyrobetaine, the immediate precursor of carnitine, was followed after injection into nursing mother rats indicated movement of carnitine from maternal liver leads to maternal plasma leads to milk leads to neonatal tissues. The above findings support the view expressed earlier that one prerequisite for the development of a high ketogenic profile in liver may be an elevation in the tissue carnitine concentration. Additional factors, however, are clearly involved as evidenced by the observation that in the fed state perfused livers from nursing mother rats synthesized ketone bodies from oleic acid at low rates compared with those seen after a 24 h fast, despite the fact that tissue carnitine levels were equally elevated in both groups. This paradox is likely related to the fact that in the fed state such livers also contained large quantities of glycogen, depletion of which through fasting was accompanied by marked acceleration of ketogenesis from oleate. The data indicate, therefore, that maximal ketogenic capacity of the liver requires for its induction an increase in carnitine coupled with a decrease in glycogen content of the tissue.
在大鼠发育期间，检测了血浆中酮体的浓度以及各种母体、胎儿和新生儿组织中肉碱的浓度。胎儿血浆中的酮水平较低，产后头24小时内增加了10倍，此后逐渐下降，到哺乳期结束时达到正常值。在新生大鼠的肝脏中观察到肉碱浓度的变化情况几乎相同。心脏组织则相反，其肉碱含量在出生时较低，随着哺乳时间的推移稳步增加至成年水平。结果表明，新生组织中肉碱的主要来源，至少在产后头2至3天，是母鼠，此时母鼠肝脏和乳汁中的肉碱含量非常高，随着哺乳的持续而下降。将肉碱的直接前体[14C]丁酸甜菜碱注射到哺乳母鼠体内后追踪其去向的实验表明，肉碱从母体肝脏进入母体血浆，再进入乳汁，最后进入新生儿组织。上述发现支持了早期提出的观点，即肝脏中高生酮状态发展的一个先决条件可能是组织肉碱浓度的升高。然而，其他因素显然也参与其中，证据是观察到，在喂食状态下，与禁食24小时后的情况相比，哺乳母鼠灌注肝脏从油酸合成酮体的速率较低，尽管两组组织中的肉碱水平同样升高。这种矛盾可能与以下事实有关，即在喂食状态下，这样的肝脏还含有大量糖原，禁食导致糖原消耗，同时油酸生酮作用明显加速。因此，数据表明，肝脏的最大生酮能力需要肉碱增加以及组织糖原含量减少才能诱导产生。
