title: Induction of peroxisomal lipid metabolism in mice fed a high-fat diet.
abstract: Peroxisomes catalyze a range of essential metabolic functions, mainly related to lipid metabolism. However, their roles in obesity have yet to be clarified. The aim of this study was to investigate the correlation between obesity and peroxisomal lipid metabolism, particularly very long-chain fatty acid (VLCFA) metabolism, gene expression of peroxisomal β-oxidation enzymes, peroxisomal ATP-binding cassette (ABC) transporter adrenoleukodystrophy (ABCD1) gene and its related gene, ABCD2, the elongation of the VLCFA (ELOVL) gene family and the transcriptional factors involved in the regulation of these genes, including peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein. These factors were analyzed in livers from mice fed a high-fat diet (HFD) or a regular diet (RD) for 20 weeks. Furthermore, the amounts of plasma saturated and unsaturated fatty acids, including VLCFAs, were measured. A HFD induced hepatic gene expression of not only hydroxysteroid 17-β dehydrogenase 4 (HSD17b4) and sterol carrier protein 2 (SCP2) in peroxisomal β-oxidation enzymes but also of ELOVL1, 2, 5 and 6, which are involved in the elongation of saturated and unsaturated VLCFAs. Furthermore, ABCD2 mRNA prominently increased in the HFD mice. The transcriptional regulator of these genes, PPARα, was also up-regulated in the HFD mice. VLCFA ratios including C24:0/C22:0, C25:0/C22:0 and C26:0/C22:0 are the most significant diagnostic markers of inherited peroxisomal diseases. These ratios were found to be low in the plasma of the HFD mice compared with the RD mice. The results suggest that HFD activates hepatic peroxisomal VLCFA metabolism, and may provide useful fundamental information to explain the role of peroxisomal function in obesity and lifestyle-related diseases.
authors.affiliation: Division of Genomic Research, Life Science Research Center, Gifu University, Gifu 501-1193, Japan.
authors.forename: Sachi
authors.initials: S
authors.lastname: Kozawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Honda
authors.forename: Naomi
authors.initials: N
authors.lastname: Kajiwara
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagase
authors.forename: Hideki
authors.initials: H
authors.lastname: Nikami
authors.forename: Yukio
authors.initials: Y
authors.lastname: Okano
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakashima
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000074061:ATP Binding Cassette Transporter, Subfamily D; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004746:Enoyl-CoA Hydratase / Q000235:genetics / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000097:blood; D005260:Female; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D064029:Peroxisomal Multifunctional Protein-2; D020675:Peroxisomes / Q000201:enzymology / Q000378:metabolism*
chemical_list: C508354:ABCD2 protein, mouse; D000074061:ATP Binding Cassette Transporter, Subfamily D; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; C552836:Abcd1 protein, mouse; D052242:Adiponectin; D002352:Carrier Proteins; D005227:Fatty Acids; D020738:Leptin; D009097:Multienzyme Complexes; D047493:PPAR alpha; C072087:sterol carrier proteins; D015067:17-Hydroxysteroid Dehydrogenases; C491288:Hsd17b4 protein, mouse; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D064029:Peroxisomal Multifunctional Protein-2; D004746:Enoyl-CoA Hydratase