title: Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice.
abstract: Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2'-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22(phox) expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22(phox) and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity.
authors.affiliation: Dept. of Pharmacology, University of Tokushima Graduate School of Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, Japan. yasuike@basic.med.tokushima-u.ac.jp
authors.forename: Soichiro
authors.initials: S
authors.lastname: Tajima
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Kaori
authors.initials: K
authors.lastname: Sawada
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamano
authors.forename: Yuya
authors.initials: Y
authors.lastname: Horinouchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kihira
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izawa-Ishizawa
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minakuchi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D052436:Adipose Tissue, White / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D015913:Chelation Therapy; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003676:Deferoxamine / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005293:Ferritins / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D007501:Iron / Q000032:analysis; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D003573:Cytochrome b Group; D016207:Cytokines; D007502:Iron Chelating Agents; D021122:Protein Subunits; D012333:RNA, Messenger; D005293:Ferritins; D007501:Iron; D019255:NADPH Oxidases; C515614:Cyba protein, mouse; D003676:Deferoxamine