Ketone-body utilization by adult and suckling rat brain in vivo

Abstract

1. Ketone-body utilization in fed and starved adult and suckling rats has been investigated by measuring arterio-venous differences across the brain. Venous blood was collected from the confluence of sinuses and arterial blood from the femoral artery in adult rats and by cardiac puncture in suckling rats. 2. During starvation the arterio-venous difference of ketone bodies increased in proportion to their concentrations in the blood and reached a value of 0.16mm at 48h. At a given concentration of the respective ketone bodies the arterio-venous differences of acetoacetate were about twice those of 3-hydroxybutyrate. 3. Fed rats in which the concentrations of ketone bodies were raised by intravenous infusion of sodium acetoacetate had the same arterio-venous differences as starved rats at corresponding ketone-body concentrations. Thus the ability of the rat brain to utilize ketone bodies is independent of the nutritional state. 4. The concentrations of glucose, acetoacetate and 3-hydroxybutyrate were much lower in the brain than in the arterial blood. The measured (blood concentration)/(brain concentration) ratio was 4.4 for glucose, 4.5 for acetoacetate and 8.1 for 3-hydroxybutyrate in 48h-starved rats. 5. The mean arterio-venous difference of glucose across the brain was 0.51mm in fed rats and 0.43mm in 96h-starved rats. 6. Conversion of glucose into lactate rose from negligible values in the fed state to 0.2mm after 48h starvation and decreased to zero after 96h starvation. 7. In 16-22-day-old suckling rats the arterio-venous differences of ketone bodies across the brain were also proportional to the ketone-body concentration, but they were about 3-4 times greater than in adult rats at the same blood ketone-body concentration. 8. Arterio-venous differences of glucose were about the same in adult and suckling rats. 9. The brain of fed suckling rats formed more lactate from glucose than fed adult rats. 10. The results indicate that ketone bodies are major metabolic fuels of the brain of the suckling rat under normal conditions.

Substrate Utilization and Brain Development

“…In all animals, there was a significant output of lactate and pyruvate from brain to blood. Similar results were obtained by Dahlquist and Persson (1976), except that in these animals, which were 20 days old, the influence of starvation on ketonaemia was greater than had been observed by Hawkins et al (1971). CBF was measured: the rate in anaesthetized infant rats was 48 ml 100 g-l min-1 and in adult rats it was 62 ml 100 g-l min-I, although the difference between the two age groups was not statistically significant.…”

“…CBF was measured: the rate in anaesthetized infant rats was 48 ml 100 g-l min-1 and in adult rats it was 62 ml 100 g-l min-I, although the difference between the two age groups was not statistically significant. In infant rats, the measured oxygen uptake was considerably less than would be required for complete oxidation of the substrates extracted, whereas this was not so in adult rats, When the arteriovenous difference values for 20-day-old rats starved for 48 h obtained by Dahlquist and Persson (1976) are compared with values ob tained by Hawkins et al (1971) for 22 day-old rats starved for 16 h, the notable difference between the two studies is the total amount of substrate taken up by the brain. Extraction values for glucose and 3-hydroxybutyrate found by Hawkins et al were about 50% lower.…”

“…The arteriovenous differences determined by Hawkins et al (1971) were obtained in anaesthe tized rats. A comparison between computed rates of total influx for 0-3-hydroxybutyrate and mea-sured rates of utilization in 21-day-old rats showed close agreement (Fig.…”

“…Transport represents total influx computed from kinetic con stants reported by and Gjedde and Crone (1975). Metabolism represents net influx estimated from the data of Hawkins et al (1971) using a CBF value of 58 ml 100 g-1 min-1.…”

The Contribution of Ketone Bodies to Basal and Activity-Dependent Neuronal Oxidation in Vivo

“…In contrast to awake rats, studies of barbiturate anesthetized and hyperketonemic (48-hour fast) adult rats consistently found higher ketone body contributions to total brain substrate oxidation, with values of 18% and 29% of total oxidation for [BHB] plasma of 0.64 mM and 2 mM, respectively. 28,29 In a study that compared 24-hour and 48-hour fasted rats under PB anesthesia, including an acute infusion of DL-BHB in 24-hour fasted rats ([BHB] plasma ¼ 0.83, 2.05, and 5.52 mM, respectively), Ruderman et al 30 found that ketone bodies accounted for 28%, 33%, and 68% respectively of total acetyl-CoA oxidation. For the halothaneanesthetized rats in the present study ([BHB] plasma ¼ 6.6 mM), 48% of acetyl-CoA oxidation was fueled by ketone bodies, which is in reasonable agreement with the above studies.…”