Curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation

Obesity has been recognized as a major risk factor for the development of chronic kidney disease, which is accompanied by increased renal inflammation, fibrosis, and apoptosis. C66 is a curcumin derivative that exerts anti-inflammatory effects by inhibiting the JNK pathway and prevents diabetic nephropathy. The present study investigates the possible protective effect of C66 on high-fat diet (HFD)-induced obesity-related glomerulopathy. Mice were fed with HFD for 8 weeks while some were treated with C66 every 2 days for 11 weeks. The HFD-fed mice developed renal dysfunction, as well as elevated triglyceride and cholesterol. Kidneys of the HFD-fed mice showed marked glomerular injuries, apoptosis, and inflammation with markedly increased cytokine production. Interestingly, treating HFD-fed mice with C66 remarkably reversed these pathological changes via inhibiting inflammation and NF-?B/JNK activation. In cultured mesangial cells, Palmitic Acid was able to activate the pro fibrotic mechanisms, apoptosis, inflammatory response, and NF-?B and JNK signaling pathways, all of which could be attenuated by C66 treatment. In all, we demonstrated that curcumin analogue C66 attenuates obesity induced renal injury by inhibiting chronic inflammation and apoptosis via targeting NF-?B and JNK. Our data suggest that C66 can be potentially used to prevent obesity-associated renal diseases warranting future investigations.

Automated summary

Obesity is a major risk factor for chronic kidney disease, but the curcumin derivative C66 has been found to attenuate obesity-induced renal injury by inhibiting chronic inflammation and apoptosis through targeting NF-κB and JNK pathways, suggesting its potential in preventing obesity-associated renal diseases.