Our previous study revealed that fish oil (FO) pre-treatment could improve the lipopolysaccharides (LPS)-induced depressive-like behavior in mice but did not alter the expression of stress hormones associated with the hypothalamic-pituitary-adrenal (HPA) axis. The exact mechanisms underlying the protective effects of FO remain elusive. Here we applied the metabolomic technique to investigate the potential involvement of FO metabolites in ameliorating depressive-like behaviors in LPS-injected mice. It revealed that LPS-injection stimulated systemic inflammation, exhausted the nicotinamide adenine dinucleotide (NAD) level in the brain, decreased energy metabolism and impaired neuronal function, which collectively contributed to depressive-like behaviors in mice. FO treatment enhanced the production of neuroprotective metabolites including taurine, hypotaurine and tyramine, decreased the generation of neurotoxic agents such as ADPR, glutamate accumulation and oxidized glutathione, and prevented the NAD exhaustion in the brain, which might underlie the beneficial effects of FO against LPS-induced inflammation and depressive-like behaviors.

中文翻译：

---

鱼油通过恢复代谢障碍减轻 LPS 诱导的小鼠炎症和抑郁样行为

我们之前的研究表明，鱼油 (FO) 预处理可以改善脂多糖 (LPS) 诱导的小鼠抑郁样行为，但不会改变与下丘脑-垂体-肾上腺 (HPA) 轴相关的应激激素的表达。FO 保护作用的确切机制仍然难以捉摸。在这里，我们应用代谢组学技术来研究 FO 代谢物在改善 LPS 注射小鼠的抑郁样行为中的潜在参与。结果表明，LPS 注射会刺激全身炎症，耗尽大脑中的烟酰胺腺嘌呤二核苷酸 (NAD) 水平，降低能量代谢并损害神经元功能，这些共同导致小鼠出现抑郁样行为。FO 治疗增强了神经保护性代谢物的产生，包括牛磺酸、