Cell Metabolism
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2025
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IF 30.9
Yu Cao,Yang Zhao,Tan Deng,Qigang Zhou,Gang Hu,Zhuang-Li Hu,Yan-Yi Jiang,Xiao-Han Yang,Fang Wang,Peng-Fei Wu,Jian-Guo Chen
Extensive research highlights impaired brain energy metabolism in neuropsychiatric disorders, whereas much less is known about the role of the peripheral metabolic state. The liver is the metabolic hub, and herein we demonstrate that hepatic hydrolysis of acetyl-coenzyme A, a central metabolic intermediate, signals the brain and helps buffer stress. Using a chronic social defeat stress paradigm in male mice, we observed a hepatic glucose-to-acetate metabolic switch, followed by a glucocorticoid-repressed transcription of the acetyl-coenzyme A hydrolase, acetyl-coenzyme A thioesterase 12, to confer stress vulnerability. Hepatic overexpression of acetyl-coenzyme A thioesterase 12 alleviated depression-like phenotypes via increasing acetate output to promote histone acetylation in the ventral hippocampus, which bolstered the expression of programmed cell death ligand 1 in astrocytes, limiting neuroinflammation and rescuing inhibitory synaptic transmission dysfunction. Our findings demonstrate that hepatic acetyl-coenzyme A hydrolysis serves as a key liver-brain axis component that regulates depression susceptibility.
研究领域:
神经生物学
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代谢学
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精神病学
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分子生物学
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免疫神经学
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表观遗传学
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肝脏病学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BEHAVIOURAL BRAIN RESEARCH
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2023
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IF 2.7
Wenjie Chen,Yiping Chen,Muhammad Shahzad Aslam,Junliang Shen,Tao Tong,Simin Yan,Wenjing Cheng,Zichun Huang,Jiawei Li,Siyu Liu,Jianguo Li,Xianjun Meng
Background Depression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats. Results The results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents. Conclusion Acupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.
研究领域:
神经科学
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精神病学
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中医
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
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IF 5.895
Shanshan Hu,Liyong Luo,Xintong Bian,Rui Hai Liu,Sibo Zhao,Yu Chen,Kang Sun,Jielin Jiang,Zhonghua Liu,Liang Zeng
Pu-erh tea is a healthy beverage rich in phytochemicals, and its effect on the risk of inducing circadian rhythm disorders (CRD) is unclear. In this study, healthy mice were given water or 0.25% (w/v) Pu-erh tea for 7 weeks, followed by a 40 day disruption of the light/dark cycle. CRD caused dysregulation of neurotransmitter secretion and clock gene oscillations, intestinal inflammation, and disruption of intestinal microbes and metabolites. Pu-erh tea boosted the indole and 5-hydroxytryptamine pathways of tryptophan metabolism via the gut–liver–brain axis. Furthermore, its metabolites (e.g., IAA, Indole, 5-HT) enhanced hepatic glycolipid metabolism and down-regulated intestinal oxidative stress by improving the brain hormone release. Tryptophan metabolites and bile acids also promoted liver lipid metabolism and inhibited intestinal inflammation (MyD88/NF-κB) via the enterohepatic circulation. Collectively, 0.25% (w/v) Pu-erh tea has the potential to prevent CRD by promoting indole and 5-HT pathways of tryptophan metabolism and signaling interactions in the gut–liver–brain axis.
研究领域:
营养学
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药理学
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分子生物学
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胃肠病学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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