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Abstract：
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.
摘要：
葡萄糖和脂质代谢是人体必需的能量来源。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，本地化,函数,和活动，在管理细胞葡萄糖和脂质代谢中起着至关重要的作用。在这些PTM中，赖氨酸甲基化是基因转录表观遗传调控的关键动态修饰。新的证据表明赖氨酸甲基化通过修饰关键酶和蛋白质显著影响葡萄糖和脂质代谢。本文就赖氨酸甲基化在糖脂代谢中的作用及其调控机制的研究进展作一综述。我们强调甲基转移酶（KMTs）和去甲基酶（KDMs）参与产生影响这些代谢途径的异常甲基化信号。此外,我们讨论了KMT和KDM抑制剂和靶向蛋白质降解剂的化学生物学和药理学，强调它们对糖尿病等疾病的临床意义，肥胖，神经退行性疾病，和癌症。这篇综述表明，靶向赖氨酸甲基化可能是治疗这些疾病的理想治疗策略。
