title: Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis.
abstract: Uric acid (UA) is the end product of purine metabolism and can reportedly act as an antioxidant. However, recently, numerous clinical and basic research approaches have revealed close associations of hyperuricemia with several disorders, particularly those comprising the metabolic syndrome. In this review, we first outline the two molecular mechanisms underlying inflammation occurrence in relation to UA metabolism; one is inflammasome activation by UA crystallization and the other involves superoxide free radicals generated by xanthine oxidase (XO). Importantly, recent studies have demonstrated the therapeutic or preventive effects of XO inhibitors against atherosclerosis and nonalcoholic steatohepatitis, which were not previously considered to be related, at least not directly, to hyperuricemia. Such beneficial effects of XO inhibitors have been reported for other organs including the kidneys and the heart. Thus, a major portion of this review focuses on the relationships between UA metabolism and the development of atherosclerosis, nonalcoholic steatohepatitis, and related disorders. Although further studies are necessary, XO inhibitors are a potentially novel strategy for reducing the risk of many forms of organ failure characteristic of the metabolic syndrome.
authors.affiliation: Division of Diabetes and Metabolism, Institute for Adult Disease, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo, Japan.
authors.forename: Akifumi
authors.identifier: 0000-0003-1385-7487
authors.initials: A
authors.lastname: Kushiyama
authors.affiliation: Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.affiliation: Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Yasuka
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamotoya
authors.affiliation: Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.affiliation: Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Moroyama, Saitama 350-0495, Japan.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D018450:Disease Progression; D005609:Free Radicals / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes; D007249:Inflammation; D024821:Metabolic Syndrome / Q000378:metabolism*; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D005609:Free Radicals; D058847:Inflammasomes; D013481:Superoxides; D014527:Uric Acid; D014969:Xanthine Oxidase