Hasselbalch S G, Madsen P L, Hageman L P, Olsen K S, Justesen N, Holm S, Paulson O B
Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
Am J Physiol. 1996 May;270(5 Pt 1):E746-51. doi: 10.1152/ajpendo.1996.270.5.E746.
During starvation, brain energy metabolism in humans changes toward oxidation of ketone bodies. To investigate if this shift is directly coupled to circulating blood concentrations of ketone bodies, we measured global cerebral blood flow (CBF) and global cerebral carbohydrate metabolism with the Kety-Schmidt technique before and during intravenous infusion with ketone bodies. During acute hyperketonemia (mean beta-hydroxybutyrate blood concentration 2.16 mM), cerebral uptake of ketones increased from 1.11 to 5.60 mumol.100 g-1.min-1, counterbalanced by an equivalent reduction of the cerebral glucose metabolism from 25.8 to 17.2 mumol.100 g-1.min-1, with the net result being an unchanged cerebral uptake of carbohydrates. In accordance with this, global cerebral oxygen metabolism was not significantly altered (144 vs. 135 mumol.100 g-1.min-1). The unchanged global cerebral metabolic activity was accompanied by a 39% increase in CBF from 51.0 to 70.9 ml.100 g-1.min-1. Regional analysis of the glucose metabolism by positron emission tomography-[18F]fluoro-2-deoxy-D-glucose indicated that mesencephalon does not oxidize ketone bodies to the same extent as the rest of the brain. It was concluded that the immediate oxidation of ketone bodies induced a decrease in cerebral glucose uptake in spite of an adequate glucose supply to the brain. Furthermore, acute hyperketonemia caused a resetting of the coupling between CBF and metabolism that could not be explained by alterations in arterial CO2 tension or pH.
在饥饿期间，人类大脑的能量代谢会转向酮体氧化。为了研究这种转变是否与循环血液中酮体的浓度直接相关，我们在用酮体进行静脉输注之前和期间，使用凯蒂-施密特技术测量了全脑血流量（CBF）和全脑碳水化合物代谢。在急性高酮血症期间（平均β-羟基丁酸血浓度为2.16 mM），大脑对酮体的摄取从1.11增加到5.60 μmol·100 g⁻¹·min⁻¹，同时大脑葡萄糖代谢相应减少，从25.8降至17.2 μmol·100 g⁻¹·min⁻¹，最终结果是大脑对碳水化合物的摄取保持不变。与此一致，全脑氧代谢没有显著改变（分别为144和135 μmol·100 g⁻¹·min⁻¹）。全脑代谢活动不变的同时，CBF增加了39%，从51.0增加到70.9 ml·100 g⁻¹·min⁻¹。通过正电子发射断层扫描-[¹⁸F]氟-2-脱氧-D-葡萄糖对葡萄糖代谢进行区域分析表明，中脑氧化酮体的程度与大脑其他部位不同。研究得出的结论是，尽管大脑有充足的葡萄糖供应，但酮体的直接氧化仍导致大脑葡萄糖摄取减少。此外，急性高酮血症导致CBF与代谢之间的耦合重新设定，这无法用动脉血二氧化碳张力或pH值的变化来解释。
