{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:32:40Z","timestamp":1778268760241,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Insomnia is a widespread problem that can lead to the occurrence of other diseases and correlates closely with sympathetic nerve hyperactivation. Obesity-induced hepatic steatosis is mediated by sympathetic overactivation. However, it remains unclear whether insomnia may cause hepatic steatosis. The goal of this study was to preliminarily investigate whether insomnia caused hepatic steatosis in rats <jats:italic>via<\/jats:italic> sympathetic hyperactivation.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A total of 32 Sprague-Dawley male rats were divided randomly into four groups: model, sympathetic denervation (Sd), estazolam, and control (eight rats\/group). Model group received sustained sleep deprivation using the modified multiple platform method. In the Sd group, rats underwent sleep deprivation after receiving Sd by 6-hydroxydopamine (6-OHDA). Estazolam group: the rats concurrently received sleep deprivation and treatment with estazolam. The other eight rats housed in cages and kept in a comfortable environment were used as control. Blood samples were obtained for analysis of plasma lipids and hepatic function. Sympathetic hyperactivation-related indexes and hepatic steatosis in liver tissues were tested.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Liver enzymes, plasma lipid levels, and hepatic steatosis were elevated in insomnia rats, and sympathetic hyperactivation was found. Insomnia-induced hepatic steatosis was effectively lowered with pharmacological ablation of the hepatic sympathetic nerves. Furthermore, the treatment of insomnia with estazolam inhibited sympathetic activation and reduced hepatic steatosis.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Sustained sleep deprivation-induced insomnia promotes hepatic steatosis in rats possibly by mediating sympathetic overactivation.<\/jats:p>","DOI":"10.3389\/fphys.2021.734009","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T17:12:21Z","timestamp":1632503541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Insomnia Promotes Hepatic Steatosis in Rats Possibly by Mediating Sympathetic Overactivation"],"prefix":"10.3389","volume":"12","author":[{"given":"Zongding","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanmei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiemin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuerganaili","family":"Aji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalibixiati","family":"Aimulajiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaxin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianhui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baopeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.mcn.2015.12.015","article-title":"Caffeine and REM sleep deprivation: effect on basal levels of signaling molecules in area CA1","volume":"71","author":"Alkadhi","year":"2016","journal-title":"Mol. Cell. Neurosci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cphy.c170012","article-title":"Triglyceride metabolism in the liver","volume":"8","author":"Alves-Bezerra","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3389\/fmed.2020.00062","article-title":"Hepatic autonomic nervous system and neurotrophic factors regulate the pathogenesis and progression of non-alcoholic fatty liver disease","volume":"7","author":"Amir","year":"2020","journal-title":"Front. Med."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1365-2869.2003.00337.x","article-title":"Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study","volume":"12","author":"Belenky","year":"2003","journal-title":"J. Sleep Res."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1001\/jama.2013.193","article-title":"Insomnia","volume":"309","author":"Buysse","year":"2013","journal-title":"JAMA"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"zsy048","DOI":"10.1093\/sleep\/zsy048","article-title":"Assessment of sympathetic neural activity in chronic insomnia: evidence for elevated cardiovascular risk","volume":"41","author":"Carter","year":"2018","journal-title":"Sleep"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1097\/HJH.0000000000001087","article-title":"Effect of renal sympathetic denervation on hepatic glucose metabolism and blood pressure in a rat model of insulin resistance","volume":"34","author":"Chen","year":"2016","journal-title":"J. Hypertens."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1002\/j.1552-4604.1991.tb03771.x","article-title":"Hypnotic efficacy of estazolam compared with flurazepam in outpatients with insomnia","volume":"31","author":"Cohn","year":"1991","journal-title":"J. Clin. Pharmacol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1368980021000902","article-title":"Higher healthy lifestyle score is associated with lower presence of non-alcoholic fatty liver disease in middle-aged and older Chinese adults: a community-based cross-sectional study","author":"Deng","year":"2021","journal-title":"Public Health Nutr."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"4192","DOI":"10.7150\/thno.21400","article-title":"Pro-inflammatory CXCR3impairs mitochondrial function in experimental non-alcoholic steatohepatitis","volume":"7","author":"Du","year":"2017","journal-title":"Theranostics"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"663889","DOI":"10.3389\/fpsyt.2021.663889","article-title":"Insomnia disorder in adult attention-deficit\/hyperactivity disorder patients: clinical, comorbidity, and treatment correlates","volume":"12","author":"Fadeuilhe","year":"2021","journal-title":"Front. Psychol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.5665\/sleep.4172","article-title":"Cognitive impairment in individuals with insomnia: clinical significance and correlates","volume":"37","author":"Fortier-Brochu","year":"2014","journal-title":"Sleep"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/978-1-4939-0897-4_3","article-title":"The enteric nervous system and gastrointestinal innervation: integrated local and central control","volume":"817","author":"Furness","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nrgastro.2017.32","article-title":"Lipid droplets and liver disease: from basic biology to clinical implications","volume":"14","author":"Gluchowski","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ejphar.2008.08.024","article-title":"Rebound insomnia induced by abrupt withdrawal of hypnotics in sleep-disturbed rats","volume":"597","author":"Hirase","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"4565","DOI":"10.1113\/JP277994","article-title":"Liver sympathetic denervation reverses obesity-induced hepatic steatosis","volume":"597","author":"Hurr","year":"2019","journal-title":"J. Physiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e12663","DOI":"10.1111\/jsr.12663","article-title":"Cardiovascular autonomic dysfunction in insomnia patients with objective short sleep duration","volume":"27","author":"Jarrin","year":"2018","journal-title":"J. Sleep Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"101138","DOI":"10.1016\/j.molmet.2020.101138","article-title":"Hepatokines and metabolism: deciphering communication from the liver","volume":"44","author":"Jensen-Cody","year":"2021","journal-title":"Mol. Metab."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.sleep.2018.11.019","article-title":"Treating insomnia improves depression, maladaptive thinking, and hyperarousal in postmenopausal women: comparing cognitive-behavioral therapy for insomnia (CBTI), sleep restriction therapy, and sleep hygiene education","volume":"55","author":"Kalmbach","year":"2019","journal-title":"Sleep Med."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1037\/abn0000645","article-title":"Sleep and circadian rhythm disruption predict persecutory symptom severity in day-to-day life: a combined actigraphy and experience sampling study","volume":"130","author":"Kammerer","year":"2021","journal-title":"J. Abnorm. Psychol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jhep.2013.03.035","article-title":"Sleep duration and quality in relation to non-alcoholic fatty liver disease in middle-aged workers and their spouses","volume":"59","author":"Kim","year":"2013","journal-title":"J. Hepatol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1016\/j.mayocp.2018.05.032","article-title":"Association of chronic insomnia with mortality and adverse renal outcomes","volume":"93","author":"Lu","year":"2018","journal-title":"Mayo Clin. Proc."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.brainres.2004.01.019","article-title":"Sleep deprivation induced by the modified multiple platform technique: quantification of sleep loss and recovery","volume":"1004","author":"Machado","year":"2004","journal-title":"Brain Res."},{"key":"ref24","first-page":"170","article-title":"Cognitive and emotional alterations in chronic insomnia","volume":"62","author":"Medrano-Martinez","year":"2016","journal-title":"Rev. Neurol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jceh.2013.06.004","article-title":"Association of sleep disorders with nonalcoholic fatty liver disease (NAFLD): a population-based study","volume":"3","author":"Mir","year":"2013","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s10865-018-9950-7","article-title":"Poor sleep quality increases symptoms of depression and anxiety in postpartum women","volume":"41","author":"Okun","year":"2018","journal-title":"J. Behav. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.bcp.2018.07.005","article-title":"Pharmacological intervention of liver triacylglycerol lipolysis: the good, the bad and the ugly","volume":"155","author":"Quiroga","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1055\/s-0039-1685524","article-title":"Lipid droplet formation and lipophagy in fatty liver disease","volume":"39","author":"Schulze","year":"2019","journal-title":"Semin. Liver Dis."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e61780","DOI":"10.1371\/journal.pone.0061780","article-title":"Neuroendocrine regulation and metabolism of glucose and lipids in primary chronic insomnia: a prospective case-control study","volume":"8","author":"Seelig","year":"2013","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1161\/HYPERTENSIONAHA.116.08212","article-title":"Arousal from sleep and sympathetic excitation during wakefulness","volume":"68","author":"Taylor","year":"2016","journal-title":"Hypertension"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1002\/bmc.202","article-title":"Rat liver and kidney catechol-O-methyltransferase activity measured by high-performance liquid chromatography with fluorescence detection","volume":"16","author":"Tsunoda","year":"2002","journal-title":"Biomed. Chromatogr."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.psyneuen.2012.05.015","article-title":"Sympathetic activity and hypothalamo-pituitary-adrenal axis activity during sleep in post-traumatic stress disorder: a study assessing polysomnography with simultaneous blood sampling","volume":"38","author":"van Liempt","year":"2013","journal-title":"Psychoneuroendocrinology"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.734009\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T17:12:25Z","timestamp":1632503545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.734009\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,24]]},"references-count":32,"alternative-id":["10.3389\/fphys.2021.734009"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.734009","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,24]]},"article-number":"734009"}}