Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0)-Treated Human Neuronal Cells (SK-NB-E)

In Alzheimer's disease, lipid alterations point towards peroxisomal dysfunctions. Indeed, a cortical accumulation of saturated very long chain fatty acids (VLCFAs: C22:0, C24:0, C26:0), substrates for peroxisomal β-oxidation, has been found in Alzheimer patients. This study was realized to investigate the effects of VLCFAs at the mitochondrial level since mitochondrial dysfunctions play crucial roles in neurodegeneration. On human neuronal SK-NB-E cells treated with C22:0, C24:0, or C26:0 (0.1–20 μM; 48 h), an inhibition of cell growth and mitochondrial dysfunctions were observed by cell counting with trypan blue, MTT assay, and measurement of mitochondrial transmembrane potential (Δψm) with DiOC6(3). A stimulation of oxidative stress was observed with DHE and MitoSOX used to quantify superoxide anion production on whole cells and at the mitochondrial level, respectively. With C24:0 and C26:0, by Western blotting, lower levels of mitochondrial complexes III and IV were detected. After staining with MitoTracker and by transmission electron microscopy used to study mitochondrial topography, mass and morphology, major changes were detected in VLCFAs treated-cells: modification of the cytoplasmic distribution of mitochondria, presence of large mitochondria, enhancement of the mitochondrial mass. Thus, VLCFAs can be potential risk factors contributing to neurodegeneration by inducing neuronal damages via mitochondrial dysfunctions

Argan oil prevents down-regulation induced by endotoxin on liver fatty acid oxidation and gluconeogenesis and on peroxisome proliferator-activated receptor gamma coactivator-1 alpha, (PGC-1alpha), peroxisome proliferator-activated receptor gamma (PPARgamma) and estrogen related receptor alpha (ERRalpha)

International audienceIn patients with sepsis, liver metabolism and its capacity to provide other organs with energeticsubstrates are impaired. This and many other pathophysiological changes seen in human patients arereproduced in mice injected with purified endotoxin (lipopolysaccharide, LPS). In the present study,down-regulation of genes involved in hepatic fatty acid oxidation (FAOx) and gluconeogenesis in miceexposed to LPS was challenged by nutritional intervention with argan oil. Mice given a standard chowsupplemented or not with either 6% (w/w) argan oil (AO) or 6% (w/w) olive oil (OO) prior toexposure to LPS were explored for liver gene expressions and enzyme activities. LPS-treated micewere protected by nutritional AO or OO supplementations against down-regulations of hepatic FAOxand gluconeogenesis. Underlying mechanisms lied in a prevention of sepsis-associated drops in hepaticexpressions of nuclear receptors PPARα and ERRα and coactivator PGC-1α. These preventive mechanisms conveyed by AO against LPS-induced metabolic dysregulation might add new therapeuticpotentialities in the management of human sepsis

Biological activities of Schottenol and Spinasterol, two natural phytosterols present in argan oil and in cactus pear seed oil, on murine miroglial BV2 cells

International audienceThe objective of this study was to evaluate the biological activities of the major phytosterols present in argan oil (AO) and in cactus seed oil (CSO) in BV2 microglial cells. Accordingly, we first determined the sterol composition of AO and CSO, showing the presence of Schottenol and Spinasterol as major sterols in AO. While in CSO, in addition to these two sterols, we found mainly another sterol, the Sitosterol. The chemical synthesis of Schottenol and Spinasterol was performed. Our results showed that these two phytosterols, as well as sterol extracts from AO or CSO, are not toxic to microglial BV2 cells. However, treatments by these phytosterols impact the mitochondrial membrane potential. Furthermore, both Schottenol and Spinasterol can modulate the gene expression of two nuclear receptors, liver X receptor (LXR)-alpha and LXR beta, their target genes ABCA1 and ABCG1. Nonetheless, only Schottenol exhibited a differential activation vis-a-vis the nuclear receptor LXR beta. Thus Schottenol and Spinasterol can be considered as new LXR agonists, which may play protective roles by the modulation of cholesterol metabolism