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After 8\u2009weeks of feeding with normal\u2010fat diet (NFD) or HFD, WT (wild type) and <jats:italic>Herp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice were measured for the body weight, liver weight and serum biochemical parameters. HE, Oil Red O, and Sirius red stainings were used to evaluate the histopathological changes of liver tissues. QRT\u2010PCR, Western blotting and Immunohistochemistry were employed to detect the mRNA and protein expression. TUNEL staining was used to observe the hepatocyte apoptosis. <jats:italic>Herp<\/jats:italic> knockout reduced the liver\/body weight ratio of mice fed with HFD with the decreased serum levels of TG, TC, HDL, LDL, GGT, Hcy, ALT, and AST. Besides, WT mice fed with HFD presented obvious steatosis, inflammation and hepatocytes ballooning, which was relieved in <jats:italic>Herp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. HFD\u2010induce NFALD mice demonstrated increased Oil Red, Sirius red, and \u03b1\u2010SMA staining than NFD\u2010induced mice, but mice in the <jats:italic>Herp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>\u2009+\u2009HFD group was lower than the WT\u2009+\u2009HFD group. HFD\u2010induce NFALD mice showed up\u2010regulated expression of Grp78, Chop, and Atf4 in liver tissues when compared with NFD fed mice. However, regarding to the mice fed with HFD, <jats:italic>Herp<\/jats:italic> deficiency decrease in the expression of Grp78, Chop, and Atf4 in liver tissues with the reduced hepatocyte apoptosis. <jats:italic>Herp<\/jats:italic> was highly expressed in HFD\u2010induced NAFLD mice. <jats:italic>Herp<\/jats:italic> knockout improved liver function and histopathological conditions with the decreased hepatocyte apoptosis and endoplasmic reticulum stress (ERS) of HFD\u2010induce NFALD mice.<\/jats:p>","DOI":"10.1002\/kjm2.12349","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T17:27:30Z","timestamp":1611077250000},"page":"487-496","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>Herp<\/i> knockout protects against nonalcoholic fatty liver disease in mice on a high fat diet"],"prefix":"10.1002","volume":"37","author":[{"given":"Zhi\u2010Xiong","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Renmin Hospital, Hubei University of Medicine  Shiyan P.R. 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