Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression
Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression
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DOI：
10.1016/j.bbi.2021.02.003
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发表时间：
2021-04-15
影响因子：
15.1
通讯作者：
Park, Ji-Yeun
中科院分区：
文献类型：
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作者：
Jung, Jeeyoun;Lee, So Min;Park, Ji-Yeun
抑郁症是一种严重的疾病，对脂质代谢和炎症反应有相当大的影响。近年来的研究表明，瘦素作为一种能量平衡的调节因子和炎症反应中的细胞因子，在抑郁症中起着重要的作用。针灸被广泛用于治疗抑郁症;然而，针灸治疗抑郁症的潜在机制和效果仍然知之甚少。本研究采用慢性束缚应激（CRS）抑郁模型，针刺KI 10、LR 8、LU 8、LR 4（AP）和非穴位（NP）进行治疗。采用脂质组学方法研究针刺对大鼠脂质代谢的影响，分析针刺前后脑内瘦素信号和免疫指标的变化，并观察针刺对大鼠旷场实验、强迫游泳实验和埋石实验中抑郁样行为的改善作用。同时，用AP针刺治疗的CRS小鼠（CRS + AP）具有显著较低水平的天冬氨酸氨基转氨酶（AST，肝损伤标志物），并且在肝脂质组学谱中表现出不同的脂质模式。特别是甘油三酯（TG）有助于改变脂质模式。与CRS小鼠相比，CRS + AP小鼠中具有相对较高不饱和脂肪酸程度的TG增加，但在NP针刺治疗的CRS小鼠（CRS + NP）中没有变化。CRS + AP小鼠血浆瘦素水平和脑（下丘脑和海马）瘦素受体阳性细胞水平分别降低和升高，而CRS和CRS + NP小鼠表现出相反的模式。这些结果表明，在AP针刺治疗减轻CRS小鼠瘦素不敏感性。此外，CRS + AP小鼠的脾脏、血浆和肝脏中促炎细胞因子如白细胞介素-1 β和肿瘤坏死因子-α的表达降低，这是减轻瘦素抵抗的结果之一。总之，这些结果表明，AP针刺治疗有效地减轻抑郁样行为，影响免疫反应，并通过减弱瘦素不敏感性改变肝脏脂质代谢。
Depression is a serious disease that has considerable impact on lipid metabolism and inflammatory responses. Recent studies have shown that leptin, which is well known as a mediator of energy homeostasis and is a cytokine in inflammatory response, plays an important role in depression. Acupuncture is widely used to treat depression; however, the underlying mechanisms and the effect of acupuncture on depression remain poorly understood. In this study, we utilized the chronic restraint stress (CRS) induced depression model and acupuncture treatment was performed at KI10, LR8, LU8, LR4 (AP) or non-acupoint (NP). Then, lipidomics was applied to investigate the effects of acupuncture on lipid metabolism and analyze leptin signals in the brain and changes of immune markers.Acupuncture treatment at AP improved depression-like behavior in an open-field test, forced swimming test, and marble burying test. Concurrently, CRS mice treated with AP acupuncture (CRS + AP) had significantly lower levels of aspartate aminotransaminase (AST, liver injury markers) and exhibited different lipid patterns in liver lipidomic profiles. In particular, triglycerides (TGs) contributed the change of lipid patterns. Compared to the CRS mice, TGs with relatively high degrees of unsaturated fatty acids increased in the CRS + AP mice, but did not change in CRS mice treated with NP acupuncture (CRS + NP). The levels of leptin in plasma and leptin receptor positive cells in the brain (hypothalamus and hippocampus) decreased and increased, respectively, in the CRS + AP mice, while opposite patterns were exhibited in the CRS and CRS + NP mice. These results indicated that acupuncture treatment at AP attenuated leptin insensitivity in CRS mice. Additionally, expression of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha were decreased in the spleen, plasma, and liver of CRS + AP mice, which was one of results of alleviation of leptin resistance. In conclusion, these results show that AP acupuncture treatment effectively alleviated the depression-like behavior, affected immune responses, and altered hepatic lipid metabolism through the attenuation of leptin insensitivity.