Lithium Chloride Promotes Lipid Accumulation through Increased Reactive Oxygen Species Generation

Lithium salts are commonly used to treat bipolar disease. Despite the frequent prescription of long-term lithium therapy, awareness of obesity, the most serious side-effect, and the mechanisms by which lithium influences lipid metabolism are largely unknown. In the present study, we gained valuable insights into the mechanisms underlying the lipogenic action of lithium by examining its effects on lipid accumulation in both cells and the zebrafish system. We have presented evidence for the first time that lithium induces lipid accumulation through stimulation of intracellular ROS generation via a GSK-3β-independent pathway. Our findings may facilitate the development of novel therapeutic targets to ameliorate side effects of lithium therapy in psychotic patients.

锂盐（lithium salts）是临床治疗双相情感障碍的常用药物。尽管长期锂盐治疗的临床处方十分普遍，但学界对其最严重的不良反应——肥胖——以及锂调控脂质代谢的具体分子机制仍知之甚少。本研究通过检测锂盐对细胞及斑马鱼（zebrafish）模型内脂质蓄积的影响，深入解析了锂盐促脂质生成作用的分子机制，获得了极具价值的研究见解。本研究首次证实，锂盐可通过不依赖糖原合成激酶3β（GSK-3β）的通路刺激细胞内活性氧（Reactive Oxygen Species, ROS）生成，进而诱导脂质蓄积。本研究结果可为开发新型治疗靶点以改善精神疾病患者锂盐治疗的不良反应提供理论支撑。