title: A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis.
abstract: A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids released via lipolysis of white adipose tissue.
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Sunwoo
authors.initials: S
authors.lastname: Chun
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Bamba
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suyama
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishijima
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.|Project on Health and Anti-aging, Kanagawa Academy of Science and Technology Life Science & Environment Research Center, Kawasaki, Kanagawa, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakai
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001835:Body Weight; D019295:Computational Biology / Q000379:methods; D004032:Diet; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D010758:Phosphorus / Q000378:metabolism*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D059467:Transcriptome
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D008055:Lipids; D010758:Phosphorus