葡萄糖和脂质代谢是身体必需的能量来源。这些代谢途径的失调是许多急性和慢性疾病的重要危险因素，包括 2 型糖尿病 (T2DM)、阿尔茨海默病 (AD)、肥胖和癌症。翻译后修饰 (PTM) 调节蛋白质结构、定位、功能和活性，在管理细胞葡萄糖和脂质代谢中发挥着至关重要的作用。在这些 PTM 中，赖氨酸甲基化是对基因转录的表观遗传调控至关重要的关键动态修饰。新的证据表明，赖氨酸甲基化通过修饰关键酶和蛋白质来显着影响葡萄糖和脂质代谢。本综述总结了目前对赖氨酸甲基化在葡萄糖和脂质代谢中的作用和调节机制的理解。我们强调甲基转移酶（KMT）和去甲基酶（KDM）参与产生影响这些代谢途径的异常甲基化信号。此外，我们还讨论了 KMT 和 KDM 抑制剂以及靶向蛋白质降解剂的化学生物学和药理学，强调它们对糖尿病、肥胖症、神经退行性疾病和癌症等疾病的临床意义。本综述表明，针对葡萄糖和脂质代谢中的赖氨酸甲基化可能是治疗这些疾病的理想治疗策略。

Glucose and lipid metabolism are essential energy sources for the body. Dysregulation in these metabolic pathways is a significant risk factor for numerous acute and chronic diseases, including type 2 diabetes (T2DM), Alzheimer's disease (AD), obesity, and cancer. Post-translational modifications (PTMs), which regulate protein structure, localization, function, and activity, play a crucial role in managing cellular glucose and lipid metabolism. Among these PTMs, lysine methylation stands out as a key dynamic modification vital for the epigenetic regulation of gene transcription. Emerging evidence indicates that lysine methylation significantly impacts glucose and lipid metabolism by modifying key enzymes and proteins. This review summarizes the current understanding of lysine methylation's role and regulatory mechanisms in glucose and lipid metabolism. We highlight the involvement of methyltransferases (KMTs) and demethylases (KDMs) in generating abnormal methylation signals affecting these metabolic pathways. Additionally, we discuss the chemical biology and pharmacology of KMT and KDM inhibitors and targeted protein degraders, emphasizing their clinical implications for diseases such as diabetes, obesity, neurodegenerative disorders, and cancers. This review suggests that targeting lysine methylation in glucose and lipid metabolism could be an ideal therapeutic strategy for treating these diseases.