Resveratrol ameliorates diabetic kidney injury by reducing lipotoxicity and modulates expression of components of the junctional adhesion molecule-like/sirtuin 1 lipid metabolism pathway

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, and previous studies have shown that lipid deposits in the kidneys can lead to diabetic kidney damage. Resveratrol reduces circulating glucose and lipid concentrations, but it is unknown whether it can reduce renal lipid deposition and lipotoxic damage by regulating local lipid metabolism. We first showed that abnormal lipid metabolism is closely related to DKD in patients. There were excessive lipid deposits in the kidneys of patients with various stages of DKD, alongside abnormal expression of the junctional adhesion molecule-like (JAML)/sirtuin 1 (Sirt1) lipid synthesis pathway (P < 0.05). Next, we fed C57BL/6J mice a high-fat diet for 12 weeks, which caused an increase in body mass, blood glucose concentration, and blood lipid concentrations; and abnormalities in renal function (P < 0.05). Resveratrol administration ameliorated the defects in circulating lipid and glucose concentrations, renal dysfunction, the renal expression of components of the JAML/Sirt1 lipid synthesis pathway, and the expression of the adipose differentiation-related protein in the mice (P < 0.05). Histological staining also showed less lipid deposition and kidney damage. Thus, resveratrol regulates the JAML/Sirt1 lipid synthesis pathway, reduces lipid deposition in the kidney, and ameliorates diabetic kidney damage.