Dehydrozingerone inhibits renal lipotoxicity in high-fat diet-induced obese mice

Abstract

Ectopic fat accumulation in the kidneys causes oxidative stress, inflammation and cell death. Dehydrozingerone (DHZ) is a curcumin analog that exhibits antitumour, antioxidant and antidiabetic effects. However, the efficacy of DHZ in diabetic nephropathy (DN) is unknown. Here, we verified the efficacy of DHZ on DN. We divided the experimental animals into three groups: regular diet, 60% high-fat diet (HFD) and HFD with DHZ for 12 weeks. We analysed levels of renal triglycerides and urinary albumin and albumin-creatinine ratio, renal morphological changes and molecular changes via real-time polymerase chain reaction and immunoblotting. Furthermore, high glucose (HG)- or palmitate (PA)-stimulated mouse mesangial cells or mouse podocytes were treated with DHZ for 24 h. As a result, DHZ markedly reduced renal glycerol accumulation and albuminuria excretion through improvement of thickened glomerular basement membrane, podocyte loss and slit diaphragm reduction. In the renal cortex in the HFD group, phospho-AMPK and nephrin expression reduced, whereas arginase 2 and CD68 expression increased; however, these changes were recovered after DHZ administration. Increased reactive oxygen species (ROS) stimulated by HG or PA in podocytes was inhibited by DHZ treatment. Collectively, these findings indicate that DHZ ameliorates DN via inhibits of lipotoxicity-induced inflammation and ROS formation.

Keywords: dehydrozingerone; diabetic nephropathy; inflammation; lipotoxicity; reactive oxygen species.