6533b834fe1ef96bd129dc98

RESEARCH PRODUCT

Molecular basis of the effects of argan oil on mitochondrial and peroxisomal metabolism of the fatty acids and inflammation

subject

description

The objective of this thesis work was to explore the molecular basis of Argan Oil (AO) effects on the mitochondrial and peroxisomal lipid metabolism and to elucidate its anti-inflammatory potential. We thus showed, initially, that the artisanal method preparation preserved the antioxidant properties of AO preventing the oxidation of the ferulic acid, by contrast to AO of commercial origin. Then, the treatment by the AO or lipopolysaccharides (LPS) of human fibroblasts, the cellular model of pseudo-neonatal adrenoleukodystrophy (P-NALD), revealed for the AO that peroxisomes proliferation is independent from the activation of the nuclear receptor PPARα and the co-activator PGC-1α. On the other side, the induction of the proliferation of peroxisomes by LPS is accompanied by an activation of both PPARα and PGC-1α. At the same time, mice treatments by AO or by the LPS showed, for the first time, the hepatic antioxidant activity of AO through the induction of the activity of the peroxisomal catalase. In addition, we showed a hypolipidemic activity of AO, by the stimulation of dehydrogenase activities (ACADs) of the mitochondrial fatty acid b-oxidation. Moreover, the AO induces the transcription of genes involved in gluconeogenesis pathway (i.e. PEPCK and G6PH). We also revealed, for the first time, the preventive effect of AO against LPS repressions of mitochondrial and peroxisomal fatty acid degradation as well as on the gluconeogenic pathway. Furthermore, the AO anti-inflammatory potential has been shown, in mice treated by LPS, through the repression of the pro-inflammatory cytokines IL-6 and TNFα and by the induction of the anti-inflammatory cytokines IL10 and IL-4. All together, our results may indicate that the Argan oil, because of its composition rich in mono and polyunsaturated fatty acids and in antioxidants as well, has a hypolipidemic and an anti-inflammatory effects, which are revealed by the regulation of the expressions of nuclear receptors and their target genes including several cytokines