{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:14:34Z","timestamp":1789470874825,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070596"],"award-info":[{"award-number":["82070596"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>\n                    Hepassocin (HPS) is a hepatokine associated with metabolic regulation and development of non\u2010alcoholic steatohepatitis (NASH). However, previous reports on HPS are controversial and its true function is not yet understood. Here, we demonstrated that hepatic HPS expression levels were upregulated in short\u2010term feeding and downregulated in long\u2010term feeding in high\u2010fat diet (HFD)\u2010 and methionine\u2010 and choline\u2010deficient (MCD) diet\u2010fed mice, as well as in genetically obese (\n                    <jats:italic>ob\/ob<\/jats:italic>\n                    ) mice. HFD\u2010 and MCD\u2010induced hepatic steatosis, inflammation, apoptosis, and fibrosis were more pronounced in\n                    <jats:italic>HPS<\/jats:italic>\n                    knockout mice than in the wild\u2010type mice. Moreover, HPS depletion aggravated HFD\u2010induced insulin resistance. By contrast, HPS administration improved MCD\u2010 or HFD\u2010induced liver phenotypes and insulin resistance in\n                    <jats:italic>HPS<\/jats:italic>\n                    knockout and wild\u2010type mice. Mechanistic studies revealed that MCD\u2010induced hepatic oxidative stress was significantly increased by HPS deficiency and could be attenuated by HPS administration. Furthermore, palmitic acid\u2010induced lipid accumulation and oxidative stress were exclusively enhanced in\n                    <jats:italic>HPS<\/jats:italic>\n                    knockout hepatocytes and diminished by HPS cotreatment. These data suggest that HPS ameliorates NASH in mice, at least in part, by inhibiting the oxidative stress. HPS expression levels are downregulated in human fatty liver tissues, suggesting that it may play an important protective role in NASH. Collectively, our findings provide clear genetic evidence that HPS has beneficial effects on the development of steatohepatitis in mice and suggest that upregulating HPS signaling may represent an effective treatment strategy for NASH.\n                  <\/jats:p>","DOI":"10.1111\/febs.16430","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T04:14:33Z","timestamp":1647231273000},"page":"5279-5304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["HPS protects the liver against steatosis, cell death, inflammation, and fibrosis in mice with steatohepatitis"],"prefix":"10.1111","volume":"289","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering School of Chemical Engineering and Technology Tianjin University  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