{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T22:26:55Z","timestamp":1774477615586,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"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":["81870583"],"award-info":[{"award-number":["81870583"]}],"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":["2018"],"award-info":[{"award-number":["2018"]}],"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":["LY17H070002"],"award-info":[{"award-number":["LY17H070002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>LMNA<\/jats:italic>\n                    gene encodes for the nuclear envelope proteins lamin A and C (lamin A\/C). A novel R133L heterozygous mutation in the\n                    <jats:italic>LMNA<\/jats:italic>\n                    gene causes atypical progeria syndrome (APS). However, the underlying mechanism remains unclear. Here, we used transgenic mice (\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>R133L\/+<\/jats:sup>\n                    mice) that expressed a heterozygous\n                    <jats:italic>LMNA<\/jats:italic>\n                    R133L mutation and 3T3\u2010L1 cell lines with stable overexpression of\n                    <jats:italic>LMNA<\/jats:italic>\n                    R133L (by lentiviral transduction) as in vivo and in vitro models to investigate the mechanisms of\n                    <jats:italic>LMNA<\/jats:italic>\n                    R133L mutations that mediate the APS phenotype. We found that a heterozygous R133L mutation in\n                    <jats:italic>LMNA<\/jats:italic>\n                    induced most of the metabolic disturbances seen in patients with this mutation, including ectopic lipid accumulation, limited subcutaneous adipose tissue (SAT) expansion, and insulin resistance. Mitochondrial dysfunction and senescence promote ectopic lipid accumulation and insulin resistance. In addition, the FLAG\u2010mediated pull\u2010down capture followed by mass spectrometry assay showed that p160 Myb\u2010binding protein (P160 MBP; Mybbp1), the critical transcriptional repressor of PGC\u20101\u03b1, was bound to lamin A\/C. Increased Mybbp1 levels in tissues and greater Mybbp1\u2010lamin A\/C binding in nuclear inhibit PGC\u20101\u03b1 activity and promotes mitochondrial dysfunction. Our findings confirm that the novel R133L heterozygous mutation in the\n                    <jats:italic>LMNA<\/jats:italic>\n                    gene caused APS are associated with marked mitochondrial respiratory chain impairment, which were induced by decreased PGC\u20101\u03b1 levels correlating with increased Mybbp1a levels in nuclear, and a senescence phenotype of the subcutaneous fat.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201252rr","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T10:45:56Z","timestamp":1672397156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mice harboring a\n                    <scp>R133L<\/scp>\n                    heterozygous mutation in\n                    <i>LMNA<\/i>\n                    exhibited ectopic lipid accumulation, aging, and mitochondrial dysfunction in adipose tissue"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-0352","authenticated-orcid":false,"given":"Ruojun","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingyi","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Biomedical Engineering and Instrument Science Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingzi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaohan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beibei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biomedical Engineering and Instrument Science Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0333-181X","authenticated-orcid":false,"given":"Fenping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/nucl.36289"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21382"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2017.12.001"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0472"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0939"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2020.10.001"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2019.10.006"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10010055"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11684-x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011226"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000500R"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309109020302"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2011.00779.x"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01350.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/21623945.2019.1640007"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02078"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14069-X"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2009.06.001"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2016.02.013"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000316893"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101073"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.09.026"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297921100102"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1652708"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01629"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192460799"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021506"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084256"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.30700"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00608.x"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00137"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4934-x"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2013.08.008"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12584"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.014"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-253971"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111598"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.14"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2020-0005"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113447"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1152204"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01232-13"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202201252RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202201252RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202201252RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T16:14:44Z","timestamp":1761668084000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202201252RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1096\/fj.202201252RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202201252rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,30]]},"assertion":[{"value":"2022-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22730"}}