Theranostics 2021; 11(10):4637-4654. doi:10.7150/thno.56082 This issue

Research Paper

Relieving lipid accumulation through UCP1 suppresses the progression of acute kidney injury by promoting the AMPK/ULK1/autophagy pathway

Wei Xiong1#, Zhiyong Xiong2#, Anni Song1, Chuntao Lei1, Chen Ye1, Chun Zhang1✉

1. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
2. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
#These authors contributed equally to this work.

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Citation:
Xiong W, Xiong Z, Song A, Lei C, Ye C, Zhang C. Relieving lipid accumulation through UCP1 suppresses the progression of acute kidney injury by promoting the AMPK/ULK1/autophagy pathway. Theranostics 2021; 11(10):4637-4654. doi:10.7150/thno.56082. Available from https://www.thno.org/v11p4637.htm

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Abstract

Graphic abstract

Rationale: Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression, and poor prognosis. Recent evidence suggests that AKI is accompanied by significant metabolic abnormalities, including alterations in lipid metabolism. However, the specific changes in lipids in AKI, and their role and regulation mechanisms are currently unclear.

Methods: Quantitative metabolomics was performed in AKI models to reveal the differences of lipid metabolism-related products. Regulated pathway was detected by western blot, qRT-PCR, immunoblot analysis and immunohistochemistry.

Results: The present study systematically analyzes the changes in lipid composition in AKI for the first time and find that the degree of lipid accumulation was highly correlated with uncoupling protein 1 (UCP1). Importantly, relieving lipid accumulation in AKI by upregulating UCP1 can significantly inhibit the progression of AKI through promoting AMPK/ULK1/autophagy pathway.

Conclusions: The present findings suggest that lipid accumulation in AKI is directly regulated by UCP1, which can activate cell autophagy and thus significantly inhibit disease progression. It will provide new ideas and targets for the treatment of AKI.

Keywords: lipids, UCP1, metabolic reprogramming, autophagy, acute kidney injury