Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

Abstract

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.

The effects of dietary fatty acid composition in the post-sucking period on metabolic alterations in adulthood: can ω3 polyunsaturated fatty acids prevent adverse programming outcomes?

“…A high-fat diet may induce obesity in mice (Kozawa et al 2011), rats (Mullen et al 2009), and humans (Boden 2011). Consistent with previous reports, the high-fat diet induced visceral adipose gain and obesity in both NL-HF and SL-HF rats.…”

Neutron-Encoded Protein Quantification by Peptide Carbamylation

“…In accordance with previously published research, proteins associated with peroxisomes were considerably up-regulated in the mice that were fed a high-fat diet (Online Resource 3) [13]. Further, expression of mitochondrial proteins was broadly down-regulated [14].…”

Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles

“…It was shown that HFD activates hepatic peroxisomal metabolism of very long-chain and branched-chain fatty acid (Kozawa et al 2011). In Zucker rats model of obesity, peroxisomal oxidation products were shown to enter mitochondria, providing the possibility to maintain lipid disposal, even under insulin resistance condition (Noland et al 2007).…”

“…During fasting, it decreased the expression of genes involved in the amino acids metabolism (Kersten et al 2001). It was upregulated in mice fed with HFD (Kozawa et al 2011). Beside metabolic processes, PPARα is also involved in regulation of inflammation processes.…”