State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, 211198, China.
Sci Rep. 2017 May 24;7(1):2335. doi: 10.1038/s41598-017-02576-5.
High fat diet (HFD)-induced metabolic disorders may lead to emotional disorders. This study aimed to explore the effect of simvastatin (SMV) and bezafibrate (BZ) on improving HFD-induced emotional changes, and tried to identify their different mechanisms. The intraperitoneal glucose tolerance test (IPGTT) was used to evaluate glucose control ability; and behavior tests including open field tests (OFT), forced swimming tests (FST), tail suspension tests (TST) and sucrose preference (SPT), were then performed to evaluate emotional changes. Serum samples were collected for the LC-MS based metabolomics analysis to explore the emotional-related differential compounds; we then evaluated the effect of the drugs. The abnormal serum metabolic profiling and emotional changes caused by HFD in mice was alleviated by SMV treatment, whereas BZ only affected the emotional disorder. The improvement of cannabinoid analogues and then produced influences on the endocannabinoid system, which may be a potential mechanism SMV action. BZ promoted tryptophan-serotonin pathway and inhibited tryptophan-kynurenine pathway, which may be its mechanism of action. Here, we proposed a shed light on the biological mechanisms underlying the observed effects, and identified an important drug candidate for the treatment of emotional disorders induced by HFD.
高脂肪饮食（HFD）诱导的代谢紊乱可能导致情绪障碍。本研究旨在探讨辛伐他汀（SMV）和苯扎贝特（BZ）改善 HFD 诱导的情绪变化的作用，并试图确定它们的不同机制。通过腹腔内葡萄糖耐量试验（IPGTT）评估葡萄糖控制能力；然后进行行为测试，包括旷场测试（OFT）、强迫游泳测试（FST）、悬尾测试（TST）和蔗糖偏好测试（SPT），以评估情绪变化。采集血清样本进行基于 LC-MS 的代谢组学分析，以探索与情绪相关的差异化合物；然后评估药物的作用。SMV 治疗可减轻 HFD 引起的小鼠血清代谢谱异常和情绪变化，而 BZ 仅影响情绪障碍。大麻素类似物的改善，然后对内源性大麻素系统产生影响，这可能是 SMV 作用的潜在机制。BZ 促进色氨酸-血清素途径，抑制色氨酸-犬尿氨酸途径，这可能是其作用机制。在这里，我们提出了一个观察到的影响的生物学机制的启示，并确定了一个重要的药物候选物，用于治疗 HFD 诱导的情绪障碍。
