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This association highlights the close relationship between psychological and physical health. The underlying mechanism of this association needs to be elucidated. In this study, a rat model of anxiety was developed via compound stress. Changes in the HPA axis and inflammatory factors in the brains of the rats were evaluated for behavioral tests and liver function, respectively. The liver metabolic profiles of the rats were characterized through liquid chromatography\u2013mass spectrometry (LC-MS). Differential metabolites were screened based on the conditions of p &lt; 0.05 and VIP &gt; 1. A pathway enrichment analysis was performed on the metabolomics data using the Ingenuity Pathway Analysis (IPA). Immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays were performed to examine the expression of the screened target epidermal growth factor receptor (EGFR) and to elucidate the pathway associated with the mechanism. The results showed the impairment of liver function among the rats in an anxiety-like state. Additionally, 61 differential metabolites in the control and anxiety groups were screened using metabolomics (p &lt; 0.05, VIP &gt; 1). The results of the IPA analysis showed that the key target was EGFR. We also found that an anxiety-like state in rats may cause liver injury through the EFGR\/PI3K\/AKT\/NF-\u03baB pathway, which can lead to the production of inflammatory factors in the liver. Our results revealed a mechanism by which anxiety-like behavior leads to liver damage in rats. The findings of this study provided new insights into the deleterious effects of psychological problems on physical health.<\/jats:p>","DOI":"10.3390\/ijms241713356","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:26:52Z","timestamp":1693297612000},"page":"13356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Unravelling the Link between Psychological Distress and Liver Disease: Insights from an Anxiety-like Rat Model and Metabolomics Analysis"],"prefix":"10.3390","volume":"24","author":[{"given":"Binjie","family":"Liu","sequence":"first","affiliation":[{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhu","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"An","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110171","DOI":"10.1016\/j.pnpbp.2020.110171","article-title":"COVID-19 pandemic impact on children and adolescents\u2019 mental health: Biological, environmental, and social factors","volume":"106","author":"Sandre","year":"2021","journal-title":"Prog. 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