Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture

Abstract

Neuron, astrocyte, and oligodendrocyte cultures which were established from developing rat brain were examined for their utilization of glucose, ketone bodies, and free fatty acids by oxidative processes. 14CO2 production was measured in these cells from [1-14C] or [6-14C]glucose; [1-14C]octanoate and [1-14C], [6-14C], or [16-14C]palmitate; and [3-14C]acetoacetate and D(-)-3-hydroxy[3-14C]butyrate. Pyruvate dehydrogenase (EC 1.2.4.1.) and 3-oxoacid-CoA transferase (EC 2.8.3.5) activities were found at high levels in each of the cell populations. Astrocytes and oligodendrocytes produced much more 14CO2 from [1-14C]glucose than from [6-14C]glucose, indicating substantial hexose monophosphate shunt activity. This process was not as active in neurons. All three cell populations readily utilized the ketone bodies for oxidative metabolism at rates 7-9 times greater than they utilized glucose. Only astrocytes were able to utilize fatty acids for 14CO2 production, and the rate of utilization was greater than that of the ketone bodies. We found that the metabolic patterns of these brain cells which were derived from the developing brain complement the nature of the diet of the suckling animal which is rich in fat and low in carbohydrate. They readily utilized the ketone bodies or fatty acids and spared glucose for processes that metabolites of fat cannot fulfill.

Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

“…As the interest in alternative metabolic substrates for metabolic therapy grows, it becomes increasingly important to document both cerebral uptake and metabolism of these substrates under various cerebral pathological states. Previous studies utilizing in vivo models have only demonstrated substrate uptake (Hawkins et al 1971;Chen et al 2000); studies demonstrating both substrate uptake and oxidation have been limited to in vitro experiments (Brandt et al 1984;Yu et al 1984;LopesCardozo et al 1986;McKenna et al 1986McKenna et al , 1994Edmond et al 1987;Westergaard et al 1994;Waniewski and Martin 1998). The present study applied a modified in vivo approach to measure both cerebral uptake and metabolism of the alternative substrate bHB and demonstrate the value of such an approach in studying cerebral injury.…”

“…Although glucose remains the primary cerebral metabolic substrate under normal conditions, there are many physiological states during which the brain's reliance on glucose shifts to alternative substrates (Owen et al 1967;Hawkins et al 1971;Dahlquist and Persson 1976;Kries and Ross 1992;Vannucci and Vannucci 2000). In vitro studies have documented uptake and oxidation of 14 C-labeled glycerol (McKenna et al 1986a) (Edmond et al 1987). However, ketone bodies such as bHB are the only endogenously circulating alternative substrates that have been shown significantly to supplement cerebral metabolism (Owen et al 1967;Hawkins et al 1971;Dahlquist and Persson 1976).…”

“…In vitro studies have documented uptake and oxidation of 14 C-labeled glycerol (McKenna et al 1986a), lactate (Brandt et al 1984;McKenna et al 1994), glutamine/glutamate (Yu et al 1984;McKenna et al 1994), citrate (Westergaard et al 1994), malate (McKenna et al 1994(McKenna et al , 1990, b-hydroxybutyrate (bHB) (Edmond et al 1987;McKenna et al 1994), acetoacetate (Lopes-Cardozo et al 1986;Waniewski and Martin 1998), as well as octanoate and palmitate (Edmond et al 1987). However, ketone bodies such as bHB are the only endogenously circulating alternative substrates that have been shown significantly to supplement cerebral metabolism (Owen et al 1967;Hawkins et al 1971;Dahlquist and Persson 1976).…”

C75, a Fatty Acid Synthase Inhibitor, Modulates AMP-activated Protein Kinase to Alter Neuronal Energy Metabolism

“…2B). Although previous studies indicated that minimal fatty acid oxidation occurs in neurons as compared with other tissues (46), experiments were performed to determine whether C75 could alter the rate of fatty acid oxidation in cortical neurons, as it did in peripheral tissues (10). The level of total fatty acid oxidation was determined by combining the 14 C-labeled acid soluble and CO 2 products obtained after the addition of [1-14 C]palmitate.…”

Evolution of the Human Brain: the key roles of DHA (omega-3 fatty acid) and Δ6-desaturase gene

“…However, at that time, this ratio (approximately 1) was very favorable (Simopoulos, 2006). Non-converted ALA undergoes aerobic b-oxidation in the astrocyte mitochondrion (Edmond et al, 1987) and is fully degraded into acetyl-CoA (Lynen's helix). The latter occurs in several synthesis pathways, including the production of ATP (Krebs cycle and the respiratory chain), lipogenesis, and cholesterogenesis (mevalonate pathway), resulting in steroid hormones, including estradiol.…”