{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:12:19Z","timestamp":1747149139207,"version":"3.40.5"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Adipose tissue dysfunction is closely associated with the development and progression of nonalcoholic fatty liver disease (NAFLD). Recent studies have implied an important role of prohibitin\u20101 (PHB1) in adipose tissue function. In the current study, we aimed to explore the function of adipocyte PHB1 in the development and progression of NAFLD. The PHB1 protein levels in adipose tissues were markedly decreased in mice fed a high\u2010fat diet (HFD) compared to those fed a chow diet. To explore the function of adipocyte PHB1 in the progression of NAFLD, mice with adipocyte\u2010specific (adipo) deletion of <jats:italic toggle=\"yes\">Phb1<\/jats:italic> (<jats:italic toggle=\"yes\">Phb1<\/jats:italic>\n                           <jats:sup>adipo\u2212\/\u2212<\/jats:sup> mice) were generated. Notably, <jats:italic toggle=\"yes\">Phb1<\/jats:italic>\n                           <jats:sup>adipo\u2212\/\u2212<\/jats:sup> mice did not develop obesity but displayed severe liver steatosis under HFD feeding. Compared to HFD\u2010fed wild\u2010type (WT) mice, HFD\u2010fed <jats:italic toggle=\"yes\">Phb1<\/jats:italic>\n                           <jats:sup>adipo\u2212\/\u2212<\/jats:sup> mice displayed dramatically lower fat mass with significantly decreased levels of total adipose tissue inflammation, including macrophage and neutrophil number as well as the expression of inflammatory mediators. To our surprise, although liver steatosis in <jats:italic toggle=\"yes\">Phb1<\/jats:italic>\n                           <jats:sup>adipo\u2212\/\u2212<\/jats:sup> mice was much more severe, liver inflammation and fibrosis were similar to WT mice after HFD feeding. RNA sequencing analyses revealed that the interferon pathway was markedly suppressed while the bone morphogenetic protein 2 pathway was significantly up\u2010regulated in the liver of HFD\u2010fed <jats:italic toggle=\"yes\">Phb1<\/jats:italic>\n                           <jats:sup>adipo\u2212\/\u2212<\/jats:sup> mice compared with HFD\u2010fed WT mice. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: HFD\u2010fed <jats:italic toggle=\"yes\">Phb1<\/jats:italic>\n                           <jats:sup>adipo\u2212\/\u2212<\/jats:sup> mice display a subtype of the lean NAFLD phenotype with severe hepatic steatosis despite low adipose mass. This subtype of the lean NAFLD phenotype has similar inflammation and fibrosis as obese NAFLD in HFD\u2010fed WT mice; this is partially due to reduced total adipose tissue inflammation and the hepatic interferon pathway.<\/jats:p>","DOI":"10.1002\/hep4.2092","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T06:41:52Z","timestamp":1665038512000},"page":"3335-3348","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Deletion of adipocyte prohibitin 1 exacerbates high\u2010fat diet\u2010induced steatosis but not liver inflammation and fibrosis"],"prefix":"10.1097","volume":"6","author":[{"given":"Xiaolin","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,Maryland,USA"},{"name":"Department of Infectious Diseases,Ruijin Hospital, Shanghai Jiao Tong University School of Medicine,Shanghai,China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung\u2010Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,Maryland,USA"},{"name":"Department of Biochemistry, College of Natural Sciences,Kangwon Institute of Inclusive Technology and Global\/Gangwon Innovative Biologics\u2010Regional Leading Research Center, Kangwon National University,Chuncheon,Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukun","family":"Guan","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4888-8670","authenticated-orcid":false,"given":"Richard","family":"Parker","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,Maryland,USA"},{"name":"Leeds Liver Unit,St James's University Hospital,Leeds,UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robim M.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,Maryland,USA"},{"name":"Department of In Vitro Toxicology and Dermato\u2010Cosmetology, Faculty of Medicine and Pharmacy,Vrije Universiteit Brussel,Brussels,Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dechun","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelly C.","family":"Lu","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine,Cedars\u2010Sinai Medical Center,Los Angeles,California,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0505-2972","authenticated-orcid":false,"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of 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