Pseudo-neonatal adrenoleukodystrophy (P-NALD) is a neurodegenerative disorder caused by acyl-CoA oxidase 1 (ACOX1) deficiency with subsequent impairment of peroxisomal fatty acid β-oxidation, accumulation of very long chain fatty acids (VLCFAs) and strong reduction in peroxisome abundance. Increase in peroxisome number has been previously suggested to improve peroxisomal disorders, and in this perspective, the present work was aimed at exploring whether modulation of peroxisomes abundance could be achieved in P-NALD fibroblasts. Here we showed that treatment with the natural Argan oil induced peroxisome proliferation in P-NALD fibroblasts. This induction was independent on activations of both nuclear receptor PPARα and its coactivator PGC-1α. Lipopolysaccharides (LPS) treatment, which caused inflammation, induced also a peroxisome proliferation that, in contrast, was dependent on activations of PPARα and PGC-1α. By its ability to induce peroxisome proliferation, Argan oil is suggested to be of potential therapeutic use in patients with P-NALD.
 Poll-The, B.T., et al. (1988) A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). American Journal of Human Genetics, 42, 422-434.
 Reddy, J.K. (2004) Peroxisome proliferators and peroxisome proliferator-activated receptor alpha: Biotic and xenobiotic sensing. American Journal of Pathology, 164, 2305-2321. doi:10.1073/pnas.1009176107
 Bagattin, A., Hugendubler, L. and Mueller, E. (2010) Transcriptional coacti-vator PGC-1α promotes peroxisomal remodeling and bioge-nesis. Proceedings of the Na- tional Academy of Sciences, 107, 20376-20381.
 Cherkaoui-Malki, M., et al. (2001) Identi-fication of novel peroxisome proliferator-activated receptor alpha (PPARα) target genes in mouse liver using cDNA microarray analysis. Gene Expression, 9, 291-304.
 Forman, B.M., Chen, J. and Evans, R.M. (1997) Hypol- ipidemic drugs, polyunsatu-rated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proceedings of the National Academy of Sciences, 94, 4312-4317. doi:10.1073/pnas.94.9.4312
 Gottlicher, M., et al. (1992) Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proceedings of the National Academy of Sciences, 89, 4653-4657. doi:10.1073/pnas.89.10.4653
 Fan, C.Y., et al. (1998) Steatohe-patitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for per- oxisome proliferator-activated receptor alpha natural lig- and metabolism. Journal of Biological Chemistry, 273, 15639-15645. doi:10.1074/jbc.273.25.15639
 Huang, J., et al. (2011) Progressive endoplasmic reticulum stress contributes to hepatocarcinogenesis in fatty acyl-CoA oxidase 1-deficient mice. The American Jour- nal of Pathology, 179, 703-713. doi:10.1016/j.ajpath.2011.04.030
 Vluggens, A., et al. (2010) Reversal of mouse Acyl-CoA oxidase 1 (ACOX1) null phenotype by human ACOX1b isoform [corrected]. Laboratory Investigation: A Journal of Technical Methods and Pathology, 90, 696-708.
 Paintlia, M.K., et al. (2008) Lipopolysaccha-ride-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteine. Experimental Neurology, 210, 560-576. doi:10.1016/j.expneurol.2007.12.011
 Baarine, M., et al. (2009) Peroxisomal and mitochondrial status of two murine oligodendrocytic cell lines (158N, 158JP): Potential models for the study of peroxisomal disorders associated with dysmyelination processes. Journal of Neurochemistry, 111, 119-131. doi:10.1111/j.1471-4159.2009.06311.x
 Schrader, M., Krieglstein, K. and Fahimi, H. D. (1998) Tubular peroxisomes in HepG2 cells: Selective induction by growth factors and ara-chidonic acid. European Journal of Cell Biology, 75, 87-96. doi:10.1016/S0171-9335(98)80051-4
 Gondcaille, C., et al. (2005) Phenylbutyrate up-regulates the adrenoleukodystro-phy-related gene as a nonclassical peroxisome proliferator. Journal of Cell Biology, 169, 93-104. doi:10.1083/jcb.200501036
 Zhang, X., et al. (2006) Peroxisome proliferator-activated receptor alpha-independent pe-roxisome proliferation. Biochemical and Biophysical Research Communications, 346, 1307-1311. doi:10.1016/j.bbrc.2006.06.042
 Gloerich, J., et al. (2005) A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPARα-dependent and -independent pathways. Journal of Lipid Research, 46, 716-726. doi:10.1194/jlr.M400337-JLR200
 DeLuca, J.G., et al. (2000) Evidence for peroxisome proliferator-activated receptor (PPAR)α-independent peroxisome proliferation: Effects of PPARγ/delta-specific agonists in PPARαlphanull mice. Moecular Pharmacology, 58, 470-476.
 Jia, Y., et al. 2003) Overexpression of peroxisome proliferator-activated recep-tor-alpha (PPARα)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydra- tase/dehydrogenase enzymes of peroxisomal beta-oxidation system. Journal of Biological Chemistry, 278, 47232- 47239. doi:10.1074/jbc.M306363200
 Contreras, M.A., et al. (2000) Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators. Hepatology, 31, 446-455. doi:10.1002/hep.510310226
 Dhaunsi, G.S., Hanevold, C.D. and Singh, I. (1994) Im pairment of peroxisomal beta-oxidation system by endotoxin treatment. Molecular and Cellular Biochemistry, 135, 187-193. doi:10.1007/BF00926522
 Khan, M., et al. (1998) Cyto-kine-induced accumulation of very long-chain fatty acids in rat C6 glial cells: Implication for X-adrenoleukodystrophy. Journal of neuro- chemistry, 71, 78-87. doi:10.1046/j.1471-4159.1998.71010078.x
 Paintlia, M.K., et al. (2008) Modulation of peroxisome proliferator-activated receptoralpha activity by N-acetyl cysteine attenuates inhibition of oligodendrocyte development in lipopolysaccharide stimulated mixed glial cultures. Journal of Neurochemistry, 105, 956-970. doi:10.1111/j.1471-4159.2007.05199.x
 Schilling, J., et al. (2011) Toll-like receptor-mediated inflammatory signaling reprograms cardiac energy metabolism by repressing peroxi-some proliferator-activated receptor gamma coactivator-1 signaling. Circulation: Heart Failure, 4, 474-482. doi:10.1161/CIRCHEARTFAILURE.110.959833