Oleoylethanolamide improves energy disposal in a cellular model of Alzheimer’s disease

Oleoylethanolamide (OEA) is an endogenous lipid mediator which is being discussed as a weight-loss drug for obesity. In addition to its homoeostatic functions, OEA has neuroprotective and anti-inflammatory capabilities. To further investigate the properties of OEA against neurodegenerative diseases, we studied the influence of OEA on mitochondrial function with a focus on mitochondrial energy metabolism in a cellular model of Alzheimer's disease (AD). SH-SY5Y-APP695 cells were used as a model for an early stage of AD. Vector-transfected SH-SY5Y-MOCK cells served as controls. Using these cells, we investigated adenosine triphosphate (ATP) production, various glucose- and fat-metabolising genes as well as fatty acid oxidation (FAO) and lactate/pyruvate levels in cells treated with OEA. Incubation with OEA showed a significant increase in ATP levels in both cell lines. Pyruvate dehydrogenase 1 gene expression was significantly decreased in SH-SY5Y-MOCK cells, whereas FAO and lactate/pyruvate ratio significantly increased in SH-SY5Y-APP695 cells. Based on the increased ATP concentration, we conclude that incubation with OEA leads to a disease-specific higher energy availability in the cells. In SH-SY5Y-MOCK cells, this seems to result from the elevated conversion of pyruvate to acetyl-CoA, whilst in SH-SY5Y-APP695 cells it may be caused by an increased lactate level and more FAO.