{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:23:02Z","timestamp":1791332582434,"version":"4.3.1"},"reference-count":23,"publisher":"American Diabetes Association","issue":"8","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,8,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder featuring near complete absence of adipose tissue. Remarkably, although the causative gene, BSCL2, has been known for several years, its molecular function and its role in adipose tissue development have not been elucidated. Therefore, we examined whether BSCL2 is involved in the regulation of adipocyte differentiation and the mechanism whereby pathogenic mutations in BSCL2 cause lipodystrophy.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014Following the characterization of BSCL2 expression in developing adipocytes, C3H10T1\/2 mesenchymal stem cells were generated in which BSCL2 expression was knocked down using short hairpin RNA (shRNA). These cells were used to investigate whether BSCL2 is required for adipogenesis. BSCL2 constructs harboring pathogenic mutations known to cause lipodystrophy were also generated and characterized.<\/jats:p>\n               <jats:p>RESULTS\u2014 BSCL2 expression was strongly induced during adipocyte differentiation, and the induction of BSCL2 expression was essential for adipogenesis to occur. The initial induction of key adipogenic transcription factors, including peroxisome proliferator\u2013activated receptor (PPAR)\u03b3 and CAAT\/enhancer-binding protein-\u03b1, was preserved in cells lacking BSCL2. However, the expression of these critical factors was not sustained, suggesting that the activity of PPAR\u03b3 was impaired. Moreover, expression of key genes mediating triglyceride synthesis, including AGPAT2, lipin\u20081, and DGAT2, was persistently reduced and lipid accumulation was inhibited. Analysis of pathogenic missense mutants of BSCL2 revealed that the amino acid substitution A212P causes aberrant targeting of BSCL2 within the cell, suggesting that subcellular localization of BSCL2 may be critical to its function.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014This study demonstrates that BSCL2 is an essential, cell-autonomous regulator of adipogenesis.<\/jats:p>","DOI":"10.2337\/db08-0184","type":"journal-article","created":{"date-parts":[[2008,5,6]],"date-time":"2008-05-06T00:43:39Z","timestamp":1210034619000},"page":"2055-2060","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":191,"title":["The Human Lipodystrophy Gene <i>BSCL2\/Seipin<\/i> May Be Essential for Normal Adipocyte Differentiation"],"prefix":"10.2337","volume":"57","author":[{"given":"Victoria A.","family":"Payne","sequence":"first","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Grimsey","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Tuthill","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Virtue","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Gray","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Dalla Nora","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert K.","family":"Semple","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"O'Rahilly","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin J.","family":"Rochford","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207583009500_R1","doi-asserted-by":"crossref","unstructured":"Agarwal AK, Garg A: Genetic disorders of adipose tissue development, differentiation, and death. 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