糖脂代谢的紊乱会导致肥胖、糖尿病和心血管疾病等代谢相关疾病。近年来,罹患代谢相关疾病的人数迅速增加,这些疾病带来越来越沉重的经济和社会负担。Sirtuin蛋白家族是一类高度保守的、NAD+依赖的蛋白去乙酰化酶和(或)ADP核糖基转移酶,在寿命调控、卡路里限制和多种糖脂代谢过程中起重要作用。细胞核中的SIRT1、SIRT6和SIRT7可以通过去乙酰化组蛋白和多种转录因子等,从而广泛地参与对糖脂代谢的调控,而线粒体中的SIRT3、SIRT4和SIRT5可以调节多种重要的线粒体内酶的活性,从而维持机体能量平衡。越来越多的研究发现,sirtuins正常活性的维持有助于延缓,甚至阻止代谢相关疾病的发生,并提示sirtuins有望成为防治这些疾病的药物靶点。
Dysregulation of glucose and lipid metabolic pathways leads to obesity, diabetes, cardiovascular disease and other metabolism related diseases. In recent years, the global prevalence of metabolic disease is rapidly increasing with devastating results for societies. Sirtuin is a conserved family of proteins with NAD^+-dependent deacetylase and/or mono-ribosyltransferase activity. Sirtuins are involved in longevity, caloric restriction and various glucose and lipid metabolic pathways. The nuclear sirtuins, SIRT1, SIRT6 and SIRT7, regulate numerous metabolic pathways through deacetylating the key transcription factors, cofactors and regulators. The mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, regulate the activity of important mitocbondrial enzymes to maintain energy homeostasis. Growing evidence indicates that sirtuins are beneficial in the prevention of metabolic-related diseases. Thus, sirtuins could be pharmacologically activated to ameliorate such diseases.