Adiponectin is a multifunctional
adipokine with
insulin-sensitizing, anti-inflammatory, and vasoprotective properties. Epidemiology studies have, however, shown that high levels of serum
adiponectin are associated with
kidney disease progression. We, therefore, examined the effect of
adiponectin administration on the progression of glomerulosclerosis in the obese diabetic (db/db) mouse, a model of type II diabetes. Recombinant human
adiponectin was administered intraperitoneally at a dose of 30 or 150 μg per day from weeks 18 to 20.
Rosiglitazone administered by gavage at 20 mg/kg
body weight (BW) daily served as a therapeutic control. Untreated uninephrectomized db/db mice developed progressive
albuminuria and glomerular matrix expansion, associated with increased expression of
transforming growth factor beta 1 (TGFβ1),
plasminogen activator inhibitor type 1 (PAI-1),
collagen I (Col I), and
fibronectin (FN). Treatment with
adiponectin at either dose reduced the increases in
albuminuria and markers of renal
fibrosis seen in db/db mice, without affecting BW and
blood glucose. Renal expressions of
tumor necrosis factor-α (TNF-α) and
monocyte-chemoattractant protein-1 (MCP-1) and urinary TNF-α levels, the markers of renal
inflammation, were increased in diabetic mice, whereas
adiponectin treatment significantly reduced the levels of these markers. Furthermore,
adiponectin obliterated the stimulatory effects of
angiotensin II (Ang II), but not the total effect of TGFβ1, on the
mRNA expression of
PAI-1, Col I, and FN by cultured glomerular mesangial cells. These observations suggest that
adiponectin treatment reduces glomerulosclerosis resulting from type II diabetes probably through its anti-inflammatory and
angiotensin-antagonistic effects. Thus,
adiponectin has therapeutic implications in the prevention of progression of
diabetic nephropathy.