{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:53:09Z","timestamp":1781869989307,"version":"3.54.5"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Natural Science Foundation of the People\u2019s Republic of China","award":["30930037"],"award-info":[{"award-number":["30930037"]}]},{"name":"National Natural Science Foundation of the People\u2019s Republic of China","award":["30821001"],"award-info":[{"award-number":["30821001"]}]},{"name":"National Natural Science Foundation of the People\u2019s Republic of China","award":["31771306"],"award-info":[{"award-number":["31771306"]}]},{"name":"National Natural Science Foundation of the People\u2019s Republic of China","award":["81700386"],"award-info":[{"award-number":["81700386"]}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["#1057887"],"award-info":[{"award-number":["#1057887"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2\/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity of glycerol-3-phosphate acyltransferases (GPATs), and increased GPAT activity may be responsible for the defective adipogenesis under seipin deficiency. Here we generated Seipin\u2212\/\u2212Gpat3\u2212\/\u2212 mice, which had mild but significant recovery of white adipose tissue mass over Seipin\u2212\/\u2212 mice. The mass of brown adipose tissue (BAT) of the Seipin\u2212\/\u2212Gpat3\u2212\/\u2212 mice was almost completely restored to normal level. Importantly, the Seipin\u2212\/\u2212Gpat3\u2212\/\u2212 mice showed significant improvement in liver steatosis and insulin sensitivity over Seipin\u2212\/\u2212 mice, which is attributable to the increased BAT mass and to the enhanced browning of the subcutaneous fat of the Seipin\u2212\/\u2212Gpat3\u2212\/\u2212 mice. Together, our results establish a functional link between seipin and GPAT3 in vivo and suggest that GPAT inhibitors may have beneficial effects on BSCL2 patients.<\/jats:p>","DOI":"10.1093\/hmg\/ddz300","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T07:44:23Z","timestamp":1575618263000},"page":"432-443","source":"Crossref","is-referenced-by-count":29,"title":["GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy"],"prefix":"10.1093","volume":"29","author":[{"given":"Mingming","family":"Gao","sequence":"first","affiliation":[{"name":"Laboratory of Lipid Metabolism, Hebei Medical University, Shijiazhuang, Hebei 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Lipid Metabolism, Hebei Medical University, Shijiazhuang, Hebei 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Lipid Metabolism, Hebei Medical University, Shijiazhuang, Hebei 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoi Yin","family":"Mak","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"key":"2020021222131445200_ref1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.med.57.022605.114424","article-title":"Genetic basis of lipodystrophies and management of metabolic complications","volume":"57","author":"Agarwal","year":"2006","journal-title":"Annu. 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Lipid Res."},{"key":"2020021222131445200_ref5","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1016\/j.febslet.2006.03.040","article-title":"Membrane topology of the human seipin protein","volume":"580","author":"Lundin","year":"2006","journal-title":"FEBS Lett."},{"key":"2020021222131445200_ref6","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1194\/jlr.M017566","article-title":"Molecular characterization of seipin and its mutants: implications for seipin in triacylglycerol synthesis","volume":"52","author":"Fei","year":"2011","journal-title":"J. Lipid Res."},{"key":"2020021222131445200_ref7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1083\/jcb.200711136","article-title":"Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast","volume":"180","author":"Fei","year":"2008","journal-title":"J. Cell Biol."},{"key":"2020021222131445200_ref8","doi-asserted-by":"crossref","first-page":"20890","DOI":"10.1073\/pnas.0704154104","article-title":"The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology","volume":"104","author":"Szymanski","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020021222131445200_ref9","doi-asserted-by":"crossref","first-page":"e1001364","DOI":"10.1371\/journal.pgen.1001364","article-title":"Tissue-autonomous function of drosophila seipin in preventing ectopic lipid droplet formation","volume":"7","author":"Tian","year":"2011","journal-title":"PLoS Genet."},{"key":"2020021222131445200_ref10","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.15252\/embj.201695170","article-title":"Seipin regulates ER-lipid droplet contacts and cargo delivery","volume":"35","author":"Salo","year":"2016","journal-title":"EMBO J."},{"key":"2020021222131445200_ref11","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.16582","article-title":"Seipin is required for converting nascent to mature lipid droplets","volume":"5","author":"Wang","year":"2016","journal-title":"Elife"},{"key":"2020021222131445200_ref12","doi-asserted-by":"crossref","first-page":"100989","DOI":"10.1016\/j.plipres.2019.100989","article-title":"The biogenesis of lipid droplets: lipids take center stage","volume":"75","author":"Gao","year":"2019","journal-title":"Prog. Lipid Res."},{"key":"2020021222131445200_ref13","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1038\/s41467-018-05278-2","article-title":"Seipin and the membrane-shaping protein Pex30 cooperate in organelle budding from the endoplasmic reticulum","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"2020021222131445200_ref14","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1038\/s41467-018-05277-3","article-title":"Lipid droplet and peroxisome biogenesis occur at the same ER subdomains","volume":"9","author":"Joshi","year":"2018","journal-title":"Nat. Commun."},{"key":"2020021222131445200_ref15","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cmet.2014.03.028","article-title":"Seipin promotes adipose tissue fat storage through the ER Ca(2)(+)-ATPase SERCA","volume":"19","author":"Bi","year":"2014","journal-title":"Cell Metab."},{"key":"2020021222131445200_ref16","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201797572","article-title":"Seipin regulates lipid homeostasis by ensuring calcium-dependent mitochondrial metabolism","volume":"37","author":"Ding","year":"2018","journal-title":"EMBO J."},{"key":"2020021222131445200_ref17","doi-asserted-by":"crossref","first-page":"e244","DOI":"10.1016\/j.devcel.2018.09.010","article-title":"Human SEIPIN binds anionic phospholipids","volume":"47","author":"Yan","year":"2018","journal-title":"Dev. 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