title: Atherogenic dyslipidemia and altered hepatic gene expression in SHRSP.Z-Leprfa/IzmDmcr rats.
abstract: We investigated lipid and lipoprotein abnormalities in SHRSP fatty rats as a new animal model of metabolic syndrome. We examined differentially expressed genes in the liver, one of the major tissues contributing to lipid metabolism. Using gel filtration high performance liquid chromatography, increased cholesterol concentrations of small particle size low-density lipoprotein (LDL) fractions were observed in SHRSP fatty rats, whereas the Zucker Fatty strain did not show a similar elevation of cholesterol content. Existence of apolipoprotein B in these fractions was confirmed by Western blotting. The small particle size of the LDL fractions was significantly decreased by a 4-week fenofibrate treatment. Microarray analysis identified seventeen genes that were significantly upregulated and ten that were significantly decreased in liver tissues of SHRSP fatty rats compared with levels in SHRSP rats. Stearoyl-coenzyme A desaturase 1, fatty acid synthase, ATP citrate lyase, and sterol regulatory element binding factor 1 genes were among the upregulated genes. These findings suggest that SHRSP fatty rats carry small dense LDL like particles which is a common lipid abnormality in the metabolic syndrome. Three of ten genes upregulated in liver tissues of SHRSP fatty rats play a role in this metabolic abnormality and are a therapeutic target of this metabolic syndrome.
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan. tueno@med.nihon-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsunemi
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Tahira
authors.forename: Taro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Junko
authors.initials: J
authors.lastname: Hiraoka-Yamamoto
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Masako
authors.initials: M
authors.lastname: Mitsumata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamori
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000235:genetics / Q000378:metabolism*; D050171:Dyslipidemias / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011924:Rats, Zucker; D013045:Species Specificity
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL