Wang Ying, Liu Tongtong, Wu Yun, Wang Lin, Ding Shaowei, Hou Baoluo, Zhao Hailing, Liu Weijing, Li Ping
China-Japan Friendship Hospital, Institute of Medical Science, Beijing, China.
Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
Int J Biol Sci. 2024 Jul 2;20(10):3710-3724. doi: 10.7150/ijbs.95216. eCollection 2024.
Lipid homeostasis is crucial for proper cellular and systemic functions. A growing number of studies confirm the importance of lipid homeostasis in diabetic kidney disease (DKD). Lipotoxicity caused by imbalance in renal lipid homeostasis can further exasperate renal injury. Large lipid deposits and lipid droplet accumulation are present in the kidneys of DKD patients. Autophagy plays a critical role in DKD lipid homeostasis and is involved in the regulation of lipid content. Inhibition or reduction of autophagy can lead to lipid accumulation, which in turn further affects autophagy. Lipophagy selectively recognizes and degrades lipids and helps to regulate cellular lipid metabolism and maintain intracellular lipid homeostasis. Therefore, we provide a systematic review of fatty acid, cholesterol, and sphingolipid metabolism, and discuss the responses of different renal intrinsic cells to imbalances in lipid homeostasis. Finally, we discuss the mechanism by which autophagy, especially lipophagy, maintains lipid homeostasis to support the development of new DKD drugs targeting lipid homeostasis.
脂质稳态对于正常的细胞和全身功能至关重要。越来越多的研究证实了脂质稳态在糖尿病肾病（DKD）中的重要性。肾脏脂质稳态失衡导致的脂毒性可进一步加剧肾损伤。DKD患者的肾脏中存在大量脂质沉积和脂滴积累。自噬在DKD脂质稳态中起关键作用，并参与脂质含量的调节。自噬的抑制或减少会导致脂质积累，进而进一步影响自噬。脂质自噬选择性地识别和降解脂质，并有助于调节细胞脂质代谢和维持细胞内脂质稳态。因此，我们对脂肪酸、胆固醇和鞘脂代谢进行了系统综述，并讨论了不同肾固有细胞对脂质稳态失衡的反应。最后，我们讨论了自噬，尤其是脂质自噬维持脂质稳态的机制，以支持开发针对脂质稳态的新型DKD药物。
