Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Theranostics. 2021 Mar 4;11(10):4637-4654. doi: 10.7150/thno.56082. eCollection 2021.
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. 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. 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. 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.
急性肾损伤（AKI）是一种起病急、进展快、预后差的严重临床急症。最近的证据表明，AKI 伴随着明显的代谢异常，包括脂质代谢的改变。然而，AKI 中脂质的具体变化及其作用和调节机制尚不清楚。本研究采用 AKI 模型进行定量代谢组学分析，以揭示脂质代谢相关产物的差异。通过 Western blot、qRT-PCR、免疫印迹分析和免疫组织化学检测调节途径。本研究首次系统分析 AKI 中脂质组成的变化，发现脂质积累程度与解偶联蛋白 1（UCP1）高度相关。重要的是，通过上调 UCP1 缓解 AKI 中的脂质积累可通过促进 AMPK/ULK1/自噬途径显著抑制 AKI 的进展。这些发现表明 AKI 中的脂质积累直接受 UCP1 调节，可激活细胞自噬，从而显著抑制疾病进展。这将为 AKI 的治疗提供新的思路和靶点。
