{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:13:32Z","timestamp":1791180812956,"version":"4.1.0"},"reference-count":34,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":2634,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"<jats:p>Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy, characterized by an almost complete loss of adipose tissue and severe insulin resistance. BSCL2 is caused by loss-of-function mutations in the BSCL2\/SEIPIN gene, which is upregulated during adipogenesis and abundantly expressed in the adipose tissue. The physiological function of SEIPIN in mature adipocytes, however, remains to be elucidated. Here, we generated adipose-specific Seipin knockout (ASKO) mice, which exhibit adipocyte hypertrophy with enlarged lipid droplets, reduced lipolysis, adipose tissue inflammation, progressive loss of white and brown adipose tissue, insulin resistance, and hepatic steatosis. Lipidomic and microarray analyses revealed accumulation\/imbalance of lipid species, including ceramides, in ASKO adipose tissue as well as increased endoplasmic reticulum stress. Interestingly, the ASKO mice almost completely phenocopy the fat-specific peroxisome proliferator\u2013activated receptor-\u03b3 (Ppar\u03b3) knockout (FKO-\u03b3) mice. Rosiglitazone treatment significantly improved a number of metabolic parameters of the ASKO mice, including insulin sensitivity. Our results therefore demonstrate a critical role of SEIPIN in maintaining lipid homeostasis and function of adipocytes and reveal an intimate relationship between SEIPIN and PPAR-\u03b3.<\/jats:p>","DOI":"10.2337\/db13-0729","type":"journal-article","created":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T02:33:47Z","timestamp":1394678027000},"page":"2320-2331","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":106,"title":["Adipose-Specific Knockout of <i>Seipin\/Bscl2<\/i> Results in Progressive Lipodystrophy"],"prefix":"10.2337","volume":"63","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Lu He Teaching Hospital of the Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby C.Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin Man","family":"Lam","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghou","family":"Shui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linkang","family":"Zhou","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Lu He Teaching Hospital of the Capital Medical University, Beijing, 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, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,6,14]]},"reference":[{"key":"2022031223271714300_B1","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 Rev Med"},{"key":"2022031223271714300_B2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/ng585","article-title":"Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13","volume":"28","author":"Magr\u00e9","year":"2001","journal-title":"Nat Genet"},{"key":"2022031223271714300_B3","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.tem.2011.02.004","article-title":"Seipin, adipogenesis and lipid 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