Sesamol Ameliorates Lipid Deposition by Maintaining the Integrity of the Lipid Droplet–Mitochondria Connection in Diabetic Nephropathy

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and an important cause of end-stage renal disease (ESRD). However, there is still a lack of effective prevention and treatment strategies in clinical practice. As a metabolic disease, DN is accompanied by renal ectopic lipid deposition, and the deposited lipids further aggravate kidney injury. However, the molecular mechanism of renal ectopic lipid deposition is currently unknown. In this study, we observed changes in lipid droplet (LD)-mitochondria connections in the kidney for the first time. Destruction of LD-mitochondria connection was involved in renal lipid deposition in the kidneys of patients and mice with DN or in high-glucose-treated HK-2 cells. Furthermore, sesamol treatment significantly increased the integrity of the LD-mitochondria connection and ameliorated renal lipotoxicity. Finally, we demonstrated that sesamol maintains the integrity of the LD-mitochondria connection by activating the peroxisome proliferator-activated receptor α (PPARα)/perilipin 5 (PLIN5) signaling pathway. Our study is the first to show that the LD-mitochondria connection may be a target for ameliorating lipid deposition in diabetic kidneys.