Institute of Clinical Medical Sciences, State Key Laboratory of Respiratory Health and Multimorbidity, China-Japan Friendship Hospital, Beijing, PR China.
College of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong, PR China.
Int J Biol Sci. 2024 Sep 9;20(12):4783-4798. doi: 10.7150/ijbs.100394. eCollection 2024.
Metabolic syndrome (MetS) is a group of metabolic abnormalities that identifies people at risk for diabetes and cardiovascular disease. MetS is characterized by lipid disorders, and non-alcoholic fatty liver disease (NAFLD) and diabetic kidney disease (DKD) are thought to be the common hepatic and renal manifestations of MetS following abnormal lipid metabolism. This paper reviews the molecular mechanisms of lipid deposition in NAFLD and DKD, highlighting the commonalities and differences in lipid metabolic pathways in NAFLD and DKD. Hepatic and renal steatosis is the result of lipid acquisition exceeding lipid processing, i.e., fatty acid uptake and lipid regeneration exceed fatty acid oxidation and export. This process is directly regulated by the interactions of nuclear receptors, transporter proteins and transcription factors, whereas pathways such as oxidative stress, autophagy, cellular pyroptosis and gut flora are also key regulatory hubs for lipid metabolic homeostasis but act slightly differently in the liver and kidney. Such insights based on liver-kidney similarities and differences offer potential options for improved treatment.
代谢综合征(MetS)是一组代谢异常,可识别出糖尿病和心血管疾病风险人群。MetS 的特征是脂质紊乱,非酒精性脂肪性肝病(NAFLD)和糖尿病肾病(DKD)被认为是脂质代谢异常后 MetS 的常见肝和肾表现。本文综述了 NAFLD 和 DKD 中脂质沉积的分子机制,强调了 NAFLD 和 DKD 中脂质代谢途径的共性和差异。肝和肾脂肪变性是脂质摄取超过脂质处理的结果,即脂肪酸摄取和脂质再生超过脂肪酸氧化和输出。这一过程直接受核受体、转运蛋白和转录因子相互作用的调节,而氧化应激、自噬、细胞焦亡和肠道菌群等途径也是脂质代谢平衡的关键调节枢纽,但在肝脏和肾脏中的作用略有不同。基于肝-肾相似性和差异性的这些见解为改善治疗提供了潜在的选择。