Objective-Obesity is recognized increasingly as a major risk factor for kidney disease. We reported previously that plasma adiponectin levels were decreased in obesity, and that adiponectin had defensive properties against type 2 diabetes and hypertension. In this study, we investigated the role of adiponectin for kidney disease in a subtotal nephrectomized mouse model. Methods and Results-Subtotal (5/6) nephrectomy was performed in adiponectin-knockout (APN-KO) and wild-type (WT) mice. The procedure resulted in significant accumulation of adiponectin in glomeruli and interstitium in the remnant kidney. Urinary albumin excretion, glomerular hypertrophy, and tubulointerstitial fibrosis were significantly worse in APN-KO mice compared with WT mice. Intraglomerular macrophage infiltration and mRNA levels of vascular cell adhesion molecule (VCAM)-1, MCP-1, tumor necrosis factor (TNF)-␣, transforming growth factor (TGF)-␤1, collagen type I/III, and NADPH oxidase components were significantly increased in KO mice compared with WT mice. Treatment of APN-KO mice with adenovirus-mediated adiponectin resulted in amelioration of albuminuria, glomerular hypertrophy, and tubulointerstitial fibrosis and reduced the elevated levels of VCAM-1, MCP-1, TNF-␣, TGF-␤1, collagen type I/III, and NADPH oxidase components mRNAs to the same levels as those in WT mice. Conclusions-Adiponectin accumulates to the injured kidney, and prevents glomerular and tubulointerstitial injury through modulating inflammation and oxidative stress. Key Words: adiponectin Ⅲ obesity Ⅲ subtotal nephrectomy Ⅲ inflammation Ⅲ oxidative stress O besity is recognized increasingly as a major risk factor for kidney disease. It has been reported that body mass index (BMI) was associated significantly with increased risk for chronic kidney disease after adjusting for the other confounders. 1 The adipose tissue produces and secretes many bioactive substances, known as adipocytokines, which directly contribute to obesity-linked metabolic and vascular diseases. Adiponectin is an adipocyte-specific plasma protein that was identified in our laboratories in a human adipose tissue cDNA library. 2 In a series of publications, we reported that physiological concentrations of human recombinant adiponectin suppressed the expression of endothelial adhesion molecules, vascular smooth muscle cell (VSMC) proliferation, macrophage-to-foam cell transformation, and tumor necrosis factor (TNF)-␣ production by macrophages in vitro. [3][4][5] We have also shown that adiponectin selectively increased the expression of tissue inhibitor of metalloproteinases, which inhibits extracellular matrix degradation and protects the vascular wall from plaque disruption, in human monocyte-derived macrophages through interleukin (IL)-10 induction, an antiinflammatory cytokine. 6 Recently, it has been reported that adiponectin exhibited cardioprotective effects after myocardial ischemia/reperfusion through the reduction of oxidative stress. 7 In human studies, we also reported the presence of hypoadip...

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.

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AimsInflammation is closely associated with the development of atherosclerosis and metabolic syndrome. Adiponectin, an adipose-derived secretory protein, possesses an anti-atherosclerotic property. The present study was undertaken to elucidate the presence and significance of adiponectin in vasculature.Methods and ResultsImmunofluorescence staining was performed in aorta of wild-type (WT) mice and demonstrated that adiponectin was co-stained with CD31. Thoracic aorta was cut through and then aortic intima was carefully shaved from aorta. Western blotting showed the existence of adiponectin protein in aortic intima, while there was no adiponectin mRNA expression. Adiponectin knockout (Adipo-KO) and WT mice were administered with a low-dose and short-term lipopolysaccharide (LPS) (1 mg/kg of LPS for 4 hours). The endothelium vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were highly increased in Adipo-KO mice compared to WT mice after LPS administration.ConclusionsAdiponectin protein exists in aortic endothelium under steady state and may protect vasculature from the initiation of atherosclerosis.

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