The effect of resveratrol on the expression of AdipoR1 in kidneys of diabetic nephropathy.

Adiponectin is an adipocyte derived protein that plays pivotal roles in anti-oxidation, anti-inflammatory and insulin-sensitizing properties by activating two receptors, AdipoR1 and AdipoR2. Recent studies have shown that the down-regulation of AdipoR1 is a known cause of diabetic nephropathy (DN). Resveratrol (Resv), a natural polyphenol, has been identified as a potent activator of forkhead transcription factor O1 (FoxO1) which can up-regulate the expression of AdipoR1. In the present study, we have investigated whether Resv can up-regulate the expression of AdipoR1 by activating FoxO1 that is in kidney of DN rats and mesangial cells (MCs) cultured in high glucose (HG, 30 mmol/L) medium. In vivo, we show that, in the renal cortex of diabetic rats, the expression of AdipoR1 was significantly reduced and correlated with an increase in the generation of malondialdehyde (MDA), Collagen IV and fibronectin proteins. However, administration with Resv significantly increased the expression of AdipoR1. This correlated with not only a decrease in generation of MDA, Collagen IV and fibronectin proteins levels but also more improved kidney pathological and biochemical indicators changes. In vitro, we show that HG-induced depression of FoxO1 activity was associated with the expression of Adipor1 in MCs. Treatment with Resv (20 μmol/L) caused an elevation in the activity of FoxO1 and a significantly increase in the expression of AdipoR1. Furthermore, inhibition of FoxO1 through short hairpin RNA markedly reduced the expression of Adipor1 in MCs cultured by Resv. In conclusion, Resv can significantly increase the expression of AdipoR1 by activating FoxO1 in diabetic kidney. These data also suggest that Resv may serve as a promising agent for preventing or treating DN.