Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis.
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.
Yamauchi
Toshimasa
T
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Japan.
Kamon
Junji
J
Waki
Hironori
H
Imai
Yasushi
Y
Shimozawa
Nobuhiro
N
Hioki
Kyouji
K
Uchida
Shoko
S
Ito
Yusuke
Y
Takakuwa
Keisuke
K
Matsui
Junji
J
Takata
Makoto
M
Eto
Kazuhiro
K
Terauchi
Yasuo
Y
Komeda
Kajuro
K
Tsunoda
Masaki
M
Murakami
Koji
K
Ohnishi
Yasuyuki
Y
Naitoh
Takeshi
T
Yamamura
Kenichi
K
Ueyama
Yoshito
Y
Froguel
Philippe
P
Kimura
Satoshi
S
Nagai
Ryozo
R
Kadowaki
Takashi
T
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
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