Substrate utilization for energy production and lipid synthesis in oligodendrocyte-enriched cultures prepared from...

The metabolism of oligodendrocytes has been studied using cultures of oligodendrocyte-enriched glial cells isolated from cerebra of 5-8-day old rats. Cultures containing 60-80% oligodendrocytes were incubated for 16h with [3-(14)C]acetoacetate, d-[3-(14)C]3-hydroxybutyrate, [U-(14)C]glucose, l-[U-(14)C]glutamine and [1-(14)C]pyruvate or [2-(14)C]pyruvate in the presence or absence of other oxidizable substrates. Labelled CO(2) was collected as an index of oxidative metabolism and the incorporation of label into total lipids, fatty acids and cholesterol was used as an index of the de novo synthesis of lipids. Glucose, acetoacetate, D-3-hydroxybutyrate, pyruvate and l-lactate were measured to determine substrate utilization and product formation under various conditions. Our results indicate that glucose is rapidly converted to lactate and is a relatively poor substrate for oxidative metabolism and lipid synthesis. Ketone bodies were used as an energy source and as precursors for the synthesis of fatty acids and cholesterol. Preferential incorporation of acetoacetate into cholesterol was not observed. Exogenous pyruvate was incorporated into both the glycerol skeleton of complex lipids and into cholesterol and fatty acids. l-Glutamine appeared to be an important substrate for the energy metabolism of these cells.