Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression.

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.

Effects of Acupuncture on Chronic Stress-Induced Depression-Like Behavior and Its Central Neural Mechanism.

Depression is a serious psychiatric disorder with an enormous socioeconomic burden, and it is commonly comorbid with pain, chronic fatigue, or other inflammatory diseases. Recent studies have shown that acupuncture is an effective therapeutic method for reducing depressive symptoms; however, the underlying mechanism remains unknown. In this study, we investigated the effects of acupuncture on chronic stress-induced depression-like behavior and its central neural mechanisms in the brain. We induced chronic restraint stress (CRS) in male C57BL/6 mice for 14 or 28 consecutive days. Acupuncture treatment was performed at KI10·LR8·LU8·LR4 or control points for 7 or 14 days. Depression-like behavior was assessed with the open field test. Then, brain neural activity involving c-Fos and serotonin-related mechanisms via the 5-HT1A and 5-HT1B receptors were investigated. Acupuncture treatment at KI10·LR8·LU8·LR4 points rescued the depressive-like behavior, while control points (LU8·LR4·HT8·LR2) and non-acupoints on the hips did not. Brain neural activity was changed in the hippocampus, cingulate cortex, motor cortex, insular cortex, thalamus, and the hypothalamus after acupuncture treatment. Acupuncture treatment increased expression of 5-HT1A receptor in the cortex, hippocampus, thalamus, and the hypothalamus, and of 5-HT1B in the cortex and thalamus. In conclusion, acupuncture treatment at KI10·LR8·LU8·LR4 was effective in alleviating the depressive-like behavior in mice, and this therapeutic effect was produced through central brain neural activity and serotonin receptor modulation.