title: Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis.
abstract: The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and beta-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor alpha. This is the first demonstration that globular adiponectin can protect against atherosclerosis in vivo. In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Junji
authors.initials: J
authors.lastname: Kamon
authors.forename: Hironori
authors.initials: H
authors.lastname: Waki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Kyouji
authors.initials: K
authors.lastname: Hioki
authors.forename: Shoko
authors.initials: S
authors.lastname: Uchida
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takakuwa
authors.forename: Junji
authors.initials: J
authors.lastname: Matsui
authors.forename: Makoto
authors.initials: M
authors.lastname: Takata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Eto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Kajuro
authors.initials: K
authors.lastname: Komeda
authors.forename: Masaki
authors.initials: M
authors.lastname: Tsunoda
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Naitoh
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamamura
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ueyama
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D052242:Adiponectin; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000378:metabolism; D008024:Ligands; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012307:Risk Factors; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001057:Apolipoproteins E; D018076:DNA, Complementary; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors