{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:09:17Z","timestamp":1760058557181,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"],"award-info":[{"award-number":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"]}]},{"name":"Space Medical Experiment Project of China Manned Space Program","award":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"],"award-info":[{"award-number":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"]}]},{"name":"National Foreign Experts Project","award":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"],"award-info":[{"award-number":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"]}]},{"name":"Key Research and Development Program of Shaanxi","award":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"],"award-info":[{"award-number":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"]}]},{"name":"Natural Science Basic Research Program of Shaanxi","award":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"],"award-info":[{"award-number":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"]}]},{"name":"Basic Scientific Research Foundation of Xi\u2019an Jiaotong University Young Academic Support Program","award":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"],"award-info":[{"award-number":["31870848","92249303","32171102","31770917","82372899","HYZHXM01023","G2022170026L","2021GXLH-Z-064","2024SF-ZDCYL-03-24","2023-JC-QN-0215","xpt012023018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The prevalence of sleep deprivation is increasing worldwide. Despite the vital roles that the liver plays in metabolism and immune response, hepatic dysfunctions in acute sleep deprivation (ASD) and chronic sleep deprivation (CSD) remain underexplored. Additionally, the effects of the newly developed chalcone analog, 1-(2,3,4-trimethoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-acrylketone (TAK), were evaluated as a potential therapeutic chemical for mitigating SD-induced hepatic damage. A modified multi-platform method was employed to prepare animal models of 72 h ASD and 21-day CSD in rats. TAK (50 mg\/kg\/day) was administered through irrigation starting one week before the experiment and continuing until the end. ASD triggered hepatic lipid accumulation and inflammation, whereas CSD resulted in pathological portal area expansion and fibrosis, with comparatively fewer disturbances in liver metabolism and inflammation. TAK effectively alleviated ASD-induced disruptions in glycogen synthesis via PI3K\/AKT\/GSK3\/GYS2 pathways, abnormal lipid accumulation via SREBP1\/FASN\/ACC, liver inflammation by balancing M1 and M2 macrophages, and liver fibrosis induced by ASD\/CSD. This study provides valuable insights into the different mechanisms of liver damage induced by severe ASD and mild CSD. Additionally, TAK has been proposed as a potential therapeutic strategy for ultimate SD-related hepatic complications.<\/jats:p>","DOI":"10.3390\/ijms26083485","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:32:53Z","timestamp":1744169573000},"page":"3485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Hepatic Metabolic Reprogramming in Acute and Chronic Sleep Deprivation and the Protective Effects of the Chalcone Analogue TAK"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-6078","authenticated-orcid":false,"given":"Yifang","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2495-8200","authenticated-orcid":false,"given":"Yachong","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranrui","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8579-6070","authenticated-orcid":false,"given":"Zhongqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiantian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1207-5037","authenticated-orcid":false,"given":"Jiankang","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9674-069X","authenticated-orcid":false,"given":"Mami","family":"Noda","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-957X","authenticated-orcid":false,"given":"Jiangang","family":"Long","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-2801","authenticated-orcid":false,"given":"Yunhua","family":"Peng","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","unstructured":"Wang, J., Zhang, Y., and Liu, N. (2024). Annual Sleep Report of China 2024, Social Sciences Academic Press."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.15585\/mmwr.mm6506a1","article-title":"Prevalence of Healthy Sleep Duration among Adults--United States, 2014","volume":"65","author":"Liu","year":"2016","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/S2468-1253(21)00169-2","article-title":"Sleep and liver disease: A bidirectional relationship","volume":"6","author":"Marjot","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E848","DOI":"10.1152\/ajpendo.00072.2018","article-title":"Mechanisms of sleep deprivation-induced hepatic steatosis and insulin resistance in mice","volume":"315","author":"Shigiyama","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jacc.2018.10.060","article-title":"Association of Sleep Duration and Quality with Subclinical Atherosclerosis","volume":"73","author":"Fuster","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.neubiorev.2016.07.004","article-title":"Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases","volume":"74","author":"Tobaldini","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biopsych.2015.05.014","article-title":"Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation","volume":"80","author":"Irwin","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.cell.2020.04.049","article-title":"Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut","volume":"181","author":"Vaccaro","year":"2020","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R1147","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.sleep.2016.06.041","article-title":"Sleep duration is associated with survival in advanced cancer patients","volume":"32","author":"Collins","year":"2017","journal-title":"Sleep. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104290","DOI":"10.1016\/j.jprot.2021.104290","article-title":"Integrated metabolomics and proteomics analysis reveals energy metabolism disorders in the livers of sleep-deprived mice","volume":"245","author":"Hu","year":"2021","journal-title":"J. Proteom."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bbi.2014.05.010","article-title":"Acute sleep deprivation in healthy young men: Impact on population diversity and function of circulating neutrophils","volume":"41","author":"Christoffersson","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1159\/000329484","article-title":"Immune outcomes of paradoxical sleep deprivation on cellular distribution in naive and lipopolysaccharide-stimulated mice","volume":"19","author":"Zager","year":"2012","journal-title":"Neuroimmunomodulation"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Huang, J., Song, P., Hang, K., Chen, Z., Zhu, Z., Zhang, Y., Xu, J., Qin, J., Wang, B., and Qu, W. (2021). Sleep Deprivation Disturbs Immune Surveillance and Promotes the Progression of Hepatocellular Carcinoma. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.727959"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000490352","article-title":"Chronic Sleep Restriction Impairs the Antitumor Immune Response in Mice","volume":"25","year":"2018","journal-title":"Neuroimmunomodulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7909","DOI":"10.1016\/j.bmc.2009.10.022","article-title":"Synthesis and biological evaluation of 3\u2019,4\u2019,5\u2019-Trimethoxychalcone analogues as inhibitors of nitric oxide production and tumor cell proliferation","volume":"17","author":"Rao","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cui, Y., Xiong, Y., Li, H., Zeng, M., Wang, Y., Li, Y., Zou, X., Lv, W., Gao, J., and Cao, R. (2021). Chalcone-Derived Nrf2 Activator Protects Cognitive Function via Maintaining Neuronal Redox Status. Antioxidants, 10.","DOI":"10.3390\/antiox10111811"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/0962-8924(96)10023-4","article-title":"GSK3: A SHAGGY frog story","volume":"6","author":"Welsh","year":"1996","journal-title":"Trends Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1353\/pbm.1998.0051","article-title":"Current perspectives on the function of sleep","volume":"41","author":"Rechtschaffen","year":"1998","journal-title":"Perspect. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbi.2015.01.004","article-title":"Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance","volume":"47","author":"Wright","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1210\/jc.2017-02459","article-title":"Local Cortisol Elevation Contributes to Endometrial Insulin Resistance in Polycystic Ovary Syndrome","volume":"103","author":"Qi","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"eadi3332","DOI":"10.1126\/science.adi3332","article-title":"Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG","volume":"383","author":"Chen","year":"2024","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","article-title":"Molecular mechanism of PPAR\u03b1 action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease","volume":"62","author":"Pawlak","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrgastro.2015.200","article-title":"Immunology in the liver\u2014From homeostasis to disease","volume":"13","author":"Heymann","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bbi.2009.06.001","article-title":"Sleep loss activates cellular markers of inflammation: Sex differences","volume":"24","author":"Irwin","year":"2010","journal-title":"Brain Behav. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11740","DOI":"10.1080\/21655979.2022.2072602","article-title":"The macrophage-associated microRNA-4715-3p\/Gasdermin D axis potentially indicates fibrosis progression in nonalcoholic fatty liver disease: Evidence from transcriptome and biological data","volume":"13","author":"Chen","year":"2022","journal-title":"Bioengineered"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S460","DOI":"10.1067\/mai.2003.108","article-title":"2. Cytokines and chemokines","volume":"111","author":"Borish","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41573-019-0040-5","article-title":"Targeting metabolic dysregulation for fibrosis therapy","volume":"19","author":"Zhao","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41575-023-00807-x","article-title":"Hepatic inflammatory responses in liver fibrosis","volume":"20","author":"Hammerich","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/hep.32299","article-title":"A strategy of vascular-targeted therapy for liver fibrosis","volume":"76","author":"Lin","year":"2022","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"Kisseleva","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cmet.2020.10.026","article-title":"The Power of Plasticity-Metabolic Regulation of Hepatic Stellate Cells","volume":"33","author":"Trivedi","year":"2021","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1725355","DOI":"10.1080\/2162402X.2020.1725355","article-title":"S100A4 promotes hepatocellular carcinogenesis by intensifying fibrosis-associated cancer cell stemness","volume":"9","author":"Li","year":"2020","journal-title":"OncoImmunology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3485\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:35Z","timestamp":1760029955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083485"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083485","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,4,8]]}}}