{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:10:53Z","timestamp":1790831453640,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-21-CE14-0024 MAMA"],"award-info":[{"award-number":["ANR-21-CE14-0024 MAMA"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity prevalence is increasing worldwide, leading to cardiometabolic morbidities. Adipocyte dysfunction, impairing white adipose tissue (WAT) expandability and metabolic flexibility, is central in the development of obesity-related metabolic complications. Rare syndromes of lipodystrophy characterized by an extreme paucity of functional adipose tissue should be considered as primary adipocyte dysfunction diseases. Berardinelli-Seip congenital lipodystrophy (BSCL) is the most severe form with a near absence of WAT associated with cardiometabolic complications such as insulin resistance, liver steatosis, dyslipidemia, and cardiomyopathy. Twenty years ago, mutations in the BSCL2 gene have been identified as the cause of BSCL in human. BSCL2 encodes seipin, an endoplasmic reticulum (ER) anchored protein whose function was unknown back then. Studies of seipin knockout mice or rats demonstrated how seipin deficiency leads to severe lipodystrophy and to cardiometabolic complications. At the cellular levels, seipin is organized in multimers that are particularly enriched at ER\/lipid droplet and ER\/mitochondria contact sites. Seipin deficiency impairs both adipocyte differentiation and mature adipocyte maintenance. Experiments using adipose tissue transplantation in seipin knockout mice and tissue-specific deletion of seipin have provided a large body of evidence that liver steatosis, cardiomyopathy, and renal injury, classical diabetic complications, are all consequences of lipodystrophy. Rare adipocyte dysfunctions such as in BSCL are the key paradigm to unravel the pathways that control adipocyte homeostasis. The knowledge gathered through the study of these pathologies may bring new strategies to maintain and improve adipose tissue expandability.<\/jats:p>","DOI":"10.3390\/ijms23020740","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Seipin Deficiency as a Model of Severe Adipocyte Dysfunction: Lessons from Rodent Models and Teaching for Human Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Jocelyne","family":"Magr\u00e9","sequence":"first","affiliation":[{"name":"Centre National de la Recherche Scientifique, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, L\u2019institut du Thorax, Universit\u00e9 de Nantes, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-5447","authenticated-orcid":false,"given":"Xavier","family":"Prieur","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, L\u2019institut du Thorax, Universit\u00e9 de Nantes, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e277","DOI":"10.1016\/S2468-2667(17)30074-9","article-title":"Overweight, obesity, and risk of cardiometabolic multimorbidity: Pooled analysis of individual-level data for 120 813 adults from 16 cohort studies from the USA and Europe","volume":"2","author":"Kuosma","year":"2017","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.bbalip.2009.12.006","article-title":"Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome\u2014An allostatic perspective","volume":"1801","author":"Virtue","year":"2010","journal-title":"Biochim. 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