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In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sprague Dawley rats were randomly divided into three groups: standard chow (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910), high-fat diet (HFD) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) or HFD combined with oral administration of myriocin (0.3\u2009mg\/kg on alternate days for 8 weeks) (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200910). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including\n                      <jats:italic>Fabp1<\/jats:italic>\n                      ,\n                      <jats:italic>Ppar\u03b1<\/jats:italic>\n                      ,\n                      <jats:italic>Cpt-1\u03b1<\/jats:italic>\n                      and\n                      <jats:italic>Acox-2<\/jats:italic>\n                      . Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      Registration ID:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.chictr.org.cn\/enIndex.aspx?proj=5584\">ChiCTR-DDT-13003983<\/jats:ext-link>\n                      . Data of registration: 13 May, 2013, retrospectively registered.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12944-019-1118-0","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T11:21:33Z","timestamp":1571656893000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis"],"prefix":"10.1186","volume":"18","author":[{"given":"Rui-Xu","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Zhi","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Hua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Xiu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Wang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Gao","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"1118_CR1","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1002\/hep.27406","volume":"60","author":"FS Wang","year":"2014","unstructured":"Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. 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Informed contents were obtained from all enrolled patients. The trial registration number is ChiCTR-DDT-13003983, Registered on 13 May 2013 (Retrospectively registered). Relevant information available at:\n                      \n                      All animal studies were approved by the Institutional Animal Care and Use Committee of Xinhua hospital and the experiments were conducted in accordance with the National Research Council Guide for Care and Use of Laboratory Animals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have approved the contents of this manuscript and agreed on the manuscript be published.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"179"}}