Utilization of ketone bodies and glucose by established neural cell lines

Abstract

The rates of utilization of [3-14C]-acetoacetate, [3-14C]-3-hydroxybutyrate, and [6-14C]-glucose were measured in four established cell lines from neuroblastoma of rat (B103) and mouse (N4TG1) and from rat astrocytoma (RGC6) and mouse oligodendroglia (G2620). The rates of incorporation of acetoacetate into lipid were 3-5 times higher than glucose in all cell lines. The incorporation of 3-hydroxybutyrate was similar to that of glucose. Thin-layer chromatography of the total lipid extracts showed the same relative rates of use of these substrates for synthesis of various phospholipids and neutral lipids. The rates of incorporation into neutral lipids and phosphatidylcholine were essentially linear for 12 hr; however, that into phosphatidylethanolamine was markedly higher in the second 6 hr interval than in the first. In all cases, the greatest percentage of label (35-50%) appeared in the phosphatidylcholine fraction. The distribution of label from each of the three substrates among the various lipids was similar in the glial cells, but there were marked differences in distribution of the two ketone bodies in the neuroblastoma lines. These cells also synthesized lipids that migrated to the same area on the chromatogram as cholesterol esters and free fatty acids. In three of the four cell lines the rates of oxidation were highest for glucose, intermediate for acetoacetate, and lowest for 3-hydroxybutyrate. The ratios of the rate of incorporation to the rate of oxidation were higher for ketone bodies (3.32 for 3-hydroxybutyrate and 5.29 for acetoacetate) than for glucose (0.41). This indicates that in these cells ketone bodies are directed toward lipid synthesis rather than oxidation, and glucose is preferentially used as an energy source.

Differential Effects of UCHL1 Modulation on Alpha-Synuclein in PD-Like Models of Alpha-Synucleinopathy

“…The rat neuroblastoma cell line B103 was used for in vitro experiments [24]. B103 cells were plated at 3.5E4 cells/well on coverslips.…”

Bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROS-induced apoptotic trigger

“…Some neuroblastomas, astrocytomas and gliomas metabolize KB's for energy and lipid synthesis (Patel et al, 1981;Roeder et al, 1982) as these tumors show high levels of activity of the three enzymes involved in KB oxidation (Fig. 2).…”

Regulation of Ketone Body Metabolism and the Role of PPARα

“…Extensive research performed on various tumor cell lines, including gliomas, suggests that they do not utilize ketone bodies as energy substrates, but rather as precursors for lipid synthesis, and further, that some lack the enzymatic machinery for ketone body metabolism [166,167,168,169,170,171,172]. Other reports demonstrate that cancer cells do express at least some ketolytic enzymes and retain the ability to metabolize ketone bodies [173,174,175,176].…”