Disruption of adiponectin causes insulin resistance and neointimal formation.
The adipocyte-derived hormone adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity, and it has been reported to exhibit putative antiatherogenic properties in vitro. In this study we generated adiponectin-deficient mice to directly investigate whether adiponectin has a physiological protective role against diabetes and atherosclerosis in vivo. Heterozygous adiponectin-deficient (adipo(+/-)) mice showed mild insulin resistance, while homozygous adiponectin-deficient (adipo(-/-)) mice showed moderate insulin resistance with glucose intolerance despite body weight gain similar to that of wild-type mice. Moreover, adipo(-/-) mice showed 2-fold more neointimal formation in response to external vascular cuff injury than wild-type mice (p = 0.01). This study provides the first direct evidence that adiponectin plays a protective role against insulin resistance and atherosclerosis in vivo.
Kubota
Naoto
N
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Terauchi
Yasuo
Y
Yamauchi
Toshimasa
T
Kubota
Tetsuya
T
Moroi
Masao
M
Matsui
Junji
J
Eto
Kazuhiro
K
Yamashita
Tokuyuki
T
Kamon
Junji
J
Satoh
Hidemi
H
Yano
Wataru
W
Froguel
Philippe
P
Nagai
Ryozo
R
Kimura
Satoshi
S
Kadowaki
Takashi
T
Noda
Tetsuo
T
D052242:Adiponectin; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006720:Homozygote; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015430:Weight Gain / Q000235:genetics
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D011506:Proteins