Accumulation of adiponectin in inflamed adipose tissues of obese mice.
OBJECTIVE
Adipose tissue inflammation plays an important role in the pathogenesis of obesity-associated complications, such as atherosclerosis. Adiponectin secreted from adipocytes has various beneficial effects including anti-inflammatory effect. Obesity often presents with hypoadiponectinemia. However, the mechanism and adiponectin movement in obesity remain uncharacterized. Here we investigated tissue distribution of adiponectin protein in lean and obese mice.


METHODS
Adiponectin protein levels were evaluated by enzyme-linked immunosorbent assay and western blotting. Adipose tissues were fractionated into mature adipocyte fraction (MAF) and stromal vascular fraction (SVF).


RESULTS
Adiponectin protein was detected not only in MAF but also in SVF, which lacks adiponectin mRNA expression, of adipose tissue remarkably. SVF adiponectin protein level was higher in obese mice than in lean mice. The mechanism of adiponectin accumulation was investigated in adiponectin-deficient (APN-KO) mice after injection of plasma from wild-type mice. These mice showed accumulation of exogenous adiponectin, which derived from wild type mice, in adipose tissues, and the adiponectin was more observed in SVF of diet induced obese APN-KO mice than lean APN-KO mice. Among the adiponectin binding proteins, T-cadherin mRNA and protein levels in SVF of obese mice were remarkably higher than in lean mice. Oxidative stress levels were also significantly higher in SVF of obese mice than lean mice. Mechanistically, H2O2 up-regulated T-cadherin mRNA level in murine macrophages.


CONCLUSIONS
The results demonstrated adiponectin targets to adipose SVF of obese mice. These findings should shed a new light on the pathology of adipose tissue inflammation and hypoadiponectinemia of obesity.
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Hideaki
H
Nakatsuji
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan. Electronic address: kkishida@imed2.med.osaka-u.ac.jp.
Ken
K
Kishida
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Ryohei
R
Sekimoto
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Noriyuki
N
Komura
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Shinji
S
Kihara
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan.
Tohru
T
Funahashi
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Iichiro
I
Shimomura
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D052242:Adiponectin; D015820:Cadherins; D017931:DNA Primers; C099972:H-cadherin; D012333:RNA, Messenger; D017382:Reactive Oxygen Species
Adiponectin; Adipose inflammation; Obesity; T-cadherin