Effect of dietary polyunsaturated fatty acids on the expression of peroxisomal ABC transporters

6533b7dafe1ef96bd126f59e

RESEARCH PRODUCT

Effect of dietary polyunsaturated fatty acids on the expression of peroxisomal ABC transporters

Franck Bonnetain Catherine Gondcaille Catherine Gondcaille Sabrina Leclercq Sabrina Leclercq Stéphane Savary Stéphane Savary Michel Narce Michel Narce Agnès André Anne Courvoisier Anne Courvoisier Jérôme Bellenger Jérôme Bellenger Jean-michel Chardigny Jeremy Skrzypski Jeremy Skrzypski Sandrine Bellenger Sandrine Bellenger

subject

Male ATP-binding cassette transporter Biology Biochemistry Dietary Fats Unsaturated Adrenal Glands Peroxisomal disorder Peroxisomes medicine Animals PPAR alpha chemistry.chemical_classification Reverse Transcriptase Polymerase Chain Reaction Peroxisomal matrix Brain General Medicine Peroxisome medicine.disease Rats Gene Expression Regulation Liver Biochemistry chemistry Docosahexaenoic acid Fatty Acids Unsaturated ACOX1 ATP-Binding Cassette Transporters Adrenoleukodystrophy Oxidation-Reduction Polyunsaturated fatty acid

description

Abstract Peroxisomal ABC transporters encoded by the ABCD genes are thought to participate in the import of specific fatty acids in the peroxisomal matrix. ABCD1 deficiency is associated with X-linked adrenoleukodystrophy (X-ALD), the most frequent peroxisomal disorder which is characterized by the accumulation of saturated very-long-chain fatty acids (VLCFA). ABCD2 (the closest homolog of ABCD1) and ABCD3 have been shown to have partial functional redundancy with ABCD1; only when overexpressed, they can compensate for VLCFA accumulation. Other lipids, for instance polyunsaturated fatty acids (PUFA), should be possible candidate substrates for the ABCD2 and ABCD3 gene products, ALDRP and PMP70 respectively. Moreover, PUFA, which are known regulators of gene expression, could therefore represent potent inducers of the ABCD genes. To test this hypothesis, littermates of n-3-deficient rats were subjected to an n-3-deficient diet or equilibrated diets containing ALA (α-linolenic acid, 18:3n-3) as unique source of n-3 fatty acids or ALA plus DHA (docosahexaenoic acid, 22:6n-3) at two different doses. We analyzed the expression of peroxisomal ABC transporters and of the peroxisomal acyl-CoA oxidase gene 1 (Acox1) in adrenals, brain and liver. Whatever the diet, we did not observe any difference in gene expression in adrenals and brain. However, the hepatic expression level of Abcd2 and Abcd3 genes was found to be significantly higher in the n-3-deficient rats than in the rats fed the ALA diet or the DHA supplemented diets. This was accompanied by important changes in hepatic fatty acid composition. In summary, the hepatic expression of Abcd2 and Abcd3 but not of Abcd1 and Abcd4 appears to be highly sensitive towards dietary PUFA. This difference could be linked to the substrate specificity of the peroxisomal ABC transporters and a specific involvement of Abcd2 and Abcd3 in PUFA metabolism.

year	journal	country	edition	language
2008-10-01	Biochimie

https://doi.org/10.1016/j.biochi.2008.05.022