Lipophagy deficiency exacerbates ectopic lipid accumulation and tubular cells injury in diabetic nephropathy |
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| Authors: | Yachun Han Shan Xiong Hao Zhao Shikun Yang Ming Yang Xuejing Zhu Na Jiang Xiaofen Xiong Peng Gao Ling Wei Ying Xiao Lin Sun |
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| Affiliation: | 1.Department of Nephrology, The Second Xiangya Hospital, Central South University, Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan China ;2.Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan China |
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| Abstract: | Autophagy-mediated lipotoxicity plays a critical role in the progression of diabetic nephropathy (DN), but the precise mechanism is not fully understood. Whether lipophagy, a selective type of autophagy participates in renal ectopic lipid deposition (ELD) and lipotoxicity in the kidney of DN is unknown. Here, decreased lipophagy, increased ELD and lipotoxcity were observed in tubular cells of patients with DN, which were accompanied with reduced expression of AdipoR1 and p-AMPK. Similar results were found in db/db mice, these changes were reversed by AdipoRon, an adiponectin receptor activator that promotes autophagy. Additionally, a significantly decreased level of lipophagy was observed in HK-2 cells, a human proximal tubular cell line treated with high glucose, which was consistent with increased lipid deposition, apoptosis and fibrosis, while were partially alleviated by AdipoRon. However, these effects were abolished by pretreatment with ULK1 inhibitor SBI-0206965, autophagy inhibitor chloroquine and enhanced by AMPK activator AICAR. These data suggested by the first time that autophagy-mediated lipophagy deficiency plays a critical role in the ELD and lipid-related renal injury of DN.Subject terms: Chronic kidney disease, Diabetes complications |
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