Increment and impairment of adiponectin in renal failure.
OBJECTIVE
Patients with chronic renal failure are at high risk of cardiovascular diseases. Previous studies in healthy population showed that hypoadiponectinemia was associated with high cardiovascular disease risk. However, plasma adiponectin (APN) levels are increased in renal dysfunction. Therefore, the clinical significance of plasma APN level in patients with moderate renal dysfunction is controversial. The aim of this study was to determine the change of plasma APN levels in a mouse model of renal failure and the loss of vasculo-protective function of APN in the presence of high cystatin C levels.


RESULTS
Subtotal (5/6) nephrectomy was performed in APN-knockout (KO) mice and wild-type (WT) mice. The procedure in WT mice resulted in the significant increase of plasma APN and cystatin C levels. The clearance rate of APN was measured by injecting plasma from WT mice into KO mice. The clearance rate was significantly decreased in subtotal nephrectomized KO mice compared with sham-operated KO mice. Adiponectin protein and mRNA levels in adipose tissue were similar to subtotal nephrectomized and sham-operated mice. In cultured endothelial cells, at a high concentration corresponding to renal failure, cystatin C abolished the suppressive effects of APN on tumour necrosis factor alpha-induced expression of monocyte adhesion molecules.


CONCLUSIONS
Plasma APN increases in chronic renal failure, at least in part due to low clearance rate. High concentrations of cystatin C abolish the vasculo-protective effect of APN.
Komura
Noriyuki
N
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Kihara
Shinji
S
Sonoda
Mina
M
Maeda
Norikazu
N
Tochino
Yoshihiro
Y
Funahashi
Tohru
T
Shimomura
Iichiro
I
D052242:Adiponectin / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D055316:Cystatin C / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
C499918:ADIPOQ protein, human; D052242:Adiponectin; C499919:Adipoq protein, mouse; D015415:Biomarkers; C525030:CST3 protein, human; D015815:Cell Adhesion Molecules; C525031:Cst3 protein, mouse; D055316:Cystatin C; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha