{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:54:42Z","timestamp":1793652882355,"version":"4.5.1"},"reference-count":42,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Innovation Special Fund of Shanghai Jiao Tong University","award":["YG2016QN18"],"award-info":[{"award-number":["YG2016QN18"]}]},{"name":"Scientific Research Fund of Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital","award":["X-2258"],"award-info":[{"award-number":["X-2258"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>As the most prevalent chemical modifications on eukaryotic mRNAs, N6-methyladenosine (m6A) methylation was reported to participate in the regulation of various metabolic diseases. This study aimed to investigate the roles of m6A methylation and methyltransferase-like16 (METTL16) in non-alcoholic fatty liver disease (NAFLD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we used a model of diet-induced NAFLD, maintaining six male C57BL\/6J mice on high-fat diet (HFD) to generate hepatic steatosis. The high-throughput sequencing and RNA sequencing were performed to identify the m6A methylation patterns and differentially expressed mRNAs in HFD mice livers. Furthermore, we detected the expression levels of m6A modify enzymes by qRT-PCR in liver tissues, and further investigated the potential role of METTL16 in NAFLD through constructing overexpression and a knockdown model of METTL16 in HepG2 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, we confirmed 15,999 m6A recurrent peaks in HFD mice and 12,322 in the control. Genes with differentially methylated m6A peaks were significantly associated with the dysregulated glucolipid metabolism and aggravated hepatic inflammatory response. In addition, we identified five genes (\n                      <jats:italic>CIDEA<\/jats:italic>\n                      ,\n                      <jats:italic>THRSP<\/jats:italic>\n                      ,\n                      <jats:italic>OSBPL3<\/jats:italic>\n                      ,\n                      <jats:italic>GDF15<\/jats:italic>\n                      and\n                      <jats:italic>LGALS1<\/jats:italic>\n                      ) that played important roles in NAFLD progression after analyzing the differentially expressed genes containing differentially methylated m6A peaks. Intriguingly, we found that the expression levels of METTL16 were substantially increased in the NAFLD model\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and further confirmed that METTL16 upregulated the expression level of lipogenic genes\n                      <jats:italic>CIDEA<\/jats:italic>\n                      in HepG2 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results indicate the critical roles of m6A methylation and METTL16 in HFD-induced mice and cell NAFLD models, which broaden people\u2019s perspectives on potential m6A-related treatments and biomarkers for NAFLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.14379","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T04:08:45Z","timestamp":1669867725000},"page":"e14379","source":"Crossref","is-referenced-by-count":28,"title":["METTL16-mediated translation of\n                    <i>CIDEA<\/i>\n                    promotes non-alcoholic fatty liver disease progression\n                    <i>via<\/i>\n                    m6A-dependent manner"],"prefix":"10.7717","volume":"10","author":[{"given":"Jinhong","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"},{"name":"Current Affiliation: Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Digestive Endoscopic Center, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huining","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Fudan University Affiliated Fifth People\u2019s Hospital, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yungai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2077-3882","authenticated-orcid":true,"given":"Long","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. 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