{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T03:01:56Z","timestamp":1785726116599,"version":"3.56.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Nonalcoholic steatohepatitis (NASH) is associated with obesity and an increased risk for liver cirrhosis and cancer. Neutral ceramidase (NcDase), which is highly expressed in the intestinal brush border of the small intestine, plays a critical role in digesting dietary sphingolipids (ceramide) to regulate the balance of sphingosine and free fatty acids. It remains unresolved whether obesity\u2010associated alteration of NcDase contributes to the manifestation of NASH. Here, we revealed that NcDase deficiency in murine models of NASH prevents hepatic inflammation and fibrosis but not steatosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>NcDase<jats:sup>\u2212\/\u2212<\/jats:sup> mice display reduced stearoyl\u2010CoA desaturase (SCD) 1 expression with a compositional decrease of monounsaturated fatty acids (MUFAs) under the different dietary conditions. We further found that NcDase is a functional regulator of intestinal B cells and influences the abundance and quality of the secretory IgA response toward commensal bacteria. Analysis of composition of the gut microbiota found that <jats:italic toggle=\"yes\">Clostridiales<\/jats:italic> colonization was increased in NcDase<jats:sup>\u2212\/\u2212<\/jats:sup> mice. The colonization of germ\u2010free mice with gut microbiota from NcDase<jats:sup>\u2212\/\u2212<\/jats:sup> mice resulted in a greater decrease in the expression of SCD1 and the level of MUFAs in the liver relative to gut microbiota from wild\u2010type littermates, which are associated with the alternation of IgA\u2010bound bacteria, including increase of <jats:italic toggle=\"yes\">Ruminococcaceae<\/jats:italic> and reduction of <jats:italic toggle=\"yes\">Desulfovibrio<\/jats:italic>. Mechanistically, NcDase is a crucial link that controls the expression of SCD1 and MUFA\u2010mediated activation of the Wnt\/\u03b2\u2010catenin. Very importantly, our experiments further demonstrated that Wnt3a stimulation can enhance the activity of NcDase in hepatocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Thus, the NcDase\u2010SCD1\u2010Wnt feedback loop promotes the diet\u2010induced steatohepatitis and fibrosis through the regulation of intestinal IgA<jats:sup>+<\/jats:sup> immune cells.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31628","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T09:07:30Z","timestamp":1605258450000},"page":"901-919","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":26,"title":["Neutral Ceramidase Mediates Nonalcoholic Steatohepatitis by Regulating Monounsaturated Fatty Acids and Gut IgA+ B Cells"],"prefix":"10.1097","volume":"73","author":[{"given":"Xuemei","family":"Gu","sequence":"first","affiliation":[{"name":"James Graham Brown Cancer Center,University of Louisville,Louisville,KY"},{"name":"The First Affiliated Hospital,Wenzhou Medical University,Wenzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghui","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Doll","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences and Neurobiology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenke","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology & Toxicology Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Siskind","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"McClain","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology & Toxicology Center,University of Louisville,Louisville,KY"},{"name":"Robley Rex VA Medical Center,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongbin","family":"Deng","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology & Toxicology Center,University of Louisville,Louisville,KY"},{"name":"Department of Surgery,University of 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