Clinical Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.
Clinical Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.
Brain Behav Immun. 2021 May;94:424-436. doi: 10.1016/j.bbi.2021.02.003. Epub 2021 Feb 16.
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.
抑郁症是一种严重的疾病，对脂质代谢和炎症反应有很大的影响。最近的研究表明，瘦素作为能量平衡的介质和炎症反应中的细胞因子，在抑郁症中起着重要作用。针灸被广泛用于治疗抑郁症；然而，其潜在机制和针灸对抑郁症的影响仍知之甚少。在这项研究中，我们利用慢性束缚应激（CRS）诱导的抑郁症模型，在 KI10、LR8、LU8、LR4（AP）或非穴位（NP）进行针灸治疗。然后，采用脂质组学方法研究针灸对脂质代谢的影响，并分析大脑中的瘦素信号和免疫标志物的变化。AP 针刺治疗改善了旷场试验、强迫游泳试验和藏珠试验中的抑郁样行为。同时，AP 针刺治疗的 CRS 小鼠（CRS+AP）的天门冬氨酸氨基转移酶（AST，肝损伤标志物）水平显著降低，肝脂质组学图谱中脂质模式发生变化。特别是，甘油三酯（TGs）导致了脂质模式的变化。与 CRS 小鼠相比，CRS+AP 小鼠的相对不饱和脂肪酸程度较高的 TGs 增加，但 CRS+NP 小鼠中的 TGs 没有变化。CRS+AP 小鼠的血浆瘦素水平和大脑（下丘脑和海马）中瘦素受体阳性细胞的瘦素水平降低和升高，而 CRS 和 CRS+NP 小鼠则表现出相反的模式。这些结果表明，AP 针刺治疗减轻了 CRS 小鼠的瘦素不敏感。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-1β和肿瘤坏死因子-α的表达降低，这是缓解瘦素抵抗的结果之一。总之，这些结果表明，AP 针刺治疗通过减轻瘦素不敏感有效缓解了抑郁样行为，影响了免疫反应，并改变了肝脏的脂质代谢。
