{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:33:33Z","timestamp":1790012013714,"version":"4.0.1"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81930108"],"award-info":[{"award-number":["81930108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000793"],"award-info":[{"award-number":["82000793"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803600"],"award-info":[{"award-number":["81803600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LBY21H070001"],"award-info":[{"award-number":["LBY21H070001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) is the most predominant form of liver diseases worldwide. Recent evidence shows that myeloid differentiation factor 2 (MD2), a protein in innate immunity and inflammation, regulates liver injury in models of NAFLD. Here, we investigated a new mechanism by which MD2 participates in the pathogenesis of experimental NAFLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Wild\u2010type,\n                      <jats:italic>Md2<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and bone marrow reconstitution mice fed with high\u2010fat diet (HFD) were used to identify the role of hepatocyte MD2 in NAFLD. Transcriptomic RNA\u2010seq and pathway enrich analysis were performed to explore the potential mechanisms of MD2. In vitro, primary hepatocytes and macrophages were cultured for mechanistic studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptome analysis and bone marrow reconstitution studies showed that hepatocyte MD2 may participate in regulating lipid metabolism in models with NAFLD. We then discovered that\n                      <jats:italic>Md2<\/jats:italic>\n                      deficiency in mice prevents HFD\u2010mediated suppression of AMP\u2010activated protein kinase (AMPK). This preservation of AMPK in\n                      <jats:italic>Md2<\/jats:italic>\n                      \u2010deficient mice was associated with normalized sterol regulatory element binding protein 1 (SREBP1) transcriptional program and a lack of lipid accumulation in both hepatocytes and liver. We then showed that hepatocyte MD2 links HFD to AMPK\/SREBP1 through TANK binding kinase 1 (TBK1). In addition, MD2\u2010increased inflammatory factor from macrophages induces hepatic TBK1 activation and AMPK suppression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hepatocyte MD2 plays a pathogenic role in NAFLD through TBK1\u2010AMPK\/SREBP1 and lipid metabolism pathway. These studies provide new insight into a non\u2010inflammatory function of MD2 and evidence for the important role of MD2 in NALFD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.777","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T03:39:04Z","timestamp":1648438744000},"source":"Crossref","is-referenced-by-count":22,"title":["MD2 deficiency prevents high\u2010fat diet\u2010induced AMPK suppression and lipid accumulation through regulating TBK1 in non\u2010alcoholic fatty liver disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Wu","family":"Luo","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Hangzhou Medical College  Hangzhou China"},{"name":"Chemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"},{"name":"Medical Research Center, The First Affiliated Hospital Wenzhou Medical University  Wenzhou 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