title: IL-1 regulates the Cyp7a1 gene and serum total cholesterol level at steady state in mice.
abstract: We examined the role of hepatic interleukin (IL)-1alpha/beta in serum total cholesterol homeostasis using male and female IL-1-knockout (KO) mice and wild-type (WT) mice. Serum total cholesterol level was higher in males than in females in WT and KO mice. The difference between sexes was closely correlated with the difference in gene expression level of cholesterol 7alpha-hydroxylase (Cyp7a1), a rate-limiting enzyme for bile acid synthesis. No significant sex difference in gene expression level of 3-hydroxy-3-methylglutaryl-CoA reductase, a rate-limiting enzyme for cholesterol synthesis, was observed in WT mice. Interestingly, the gene expression level of hepatic Cyp7a1 was lower in KO mice than in sex-matched WT mice, while the serum total cholesterol level was the opposite. The present findings demonstrate that IL-1alpha and IL-1beta are positive regulators for the Cyp7a1 gene in steady-state mice and that Cyp7a1 is one of the factors that mediate the difference in serum total cholesterol level between sexes.
authors.affiliation: Animal Genome Research Unit, Division of Animal Sciences, National Institute of Agrobiological Sciences, Kannondai 2-1-2, Tsukuba 305-8602, Japan. misaki@affrc.go.jp
authors.forename: Misaki
authors.initials: M
authors.lastname: Kojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashino
authors.forename: Takemi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Masashi
authors.initials: M
authors.lastname: Sekimoto
authors.forename: Masakuni
authors.initials: M
authors.lastname: Degawa
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000235:genetics; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012737:Sex Factors
chemical_list: D001647:Bile Acids and Salts; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse