{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:10:37Z","timestamp":1790831437314,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>The term Multiple Symmetric Lipomatosis (MSL) describes a heterogeneous group of rare monogenic disorders and multifactorial conditions, characterized by upper-body adipose masses. Biallelic variants in <jats:italic>LIPE<\/jats:italic> encoding hormone-sensitive lipase (HSL), a key lipolytic enzyme, were implicated in three families worldwide. We aimed to further delineate <jats:italic>LIPE<\/jats:italic>-related clinical features and pathophysiological determinants.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>A gene panel was used to identify pathogenic variants. The disease features were reviewed at the French lipodystrophy reference center. The immunohistological, ultrastructural, and protein expression characteristics of lipomatous tissue were determined in surgical samples from one patient. The functional impact of variants was investigated by developing a model of adipose stem cells (ASCs) isolated from lipomatous tissue.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>We identified new biallelic <jats:italic>LIPE<\/jats:italic> null variants in three unrelated patients referred for MSL and\/or partial lipodystrophy. The hallmarks of the disease, appearing in adulthood, included lower-limb lipoatrophy, upper-body and abdominal pseudo-lipomatous masses, diabetes and\/or insulin resistance, hypertriglyceridemia, liver steatosis, high blood pressure, and neuromuscular manifestations. Ophthalmological investigations revealed numerous auto-fluorescent drusen-like retinal deposits in all patients. Lipomatous tissue and patient ASCs showed loss of HSL and decreased expression of adipogenic and mature adipocyte markers. <jats:italic>LIPE<\/jats:italic>-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conslusions<\/jats:title>\n<jats:p>Biallelic<jats:italic> LIPE<\/jats:italic> null variants result in a multisystemic disease requiring multidisciplinary care. Loss of HSL expression impairs adipocyte differentiation, consistent with the lipodystrophy\/MSL phenotype and associated metabolic complications. Detailed ophthalmological examination could reveal retinal damage, further pointing to the nervous tissue as an important disease target.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-1013","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T13:41:32Z","timestamp":1603719692000},"page":"155-168","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":44,"title":["LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells"],"prefix":"10.1093","volume":"184","author":[{"given":"Camille","family":"Sollier","sequence":"first","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Capel","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Aguilhon","sequence":"additional","affiliation":[{"name":"2CHU de Montpellier, H\u00f4pital Lapeyronie, Service d\u2019Endocrinologie-Diab\u00e9tologie-Nutrition, and Institut de G\u00e9nomique Fonctionnelle, CNRS, INSERM, Universit\u00e9 de Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasily","family":"Smirnov","sequence":"additional","affiliation":[{"name":"3CHU de Lille, Exploration de la Vision et Neuro-Ophtalmologie, Lille, France"},{"name":"4Universit\u00e9 de Lille, Facult\u00e9 de M\u00e9decine, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Auclair","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Douillard","sequence":"additional","affiliation":[{"name":"5Hopital Huriez-CHU Lille, Service d\u2019Endocrinologie-Diab\u00e9tologie-M\u00e9tabolisme, et H\u00f4pital Jeanne de Flandres, Centre de R\u00e9f\u00e9rence des Maladies H\u00e9r\u00e9ditaires du M\u00e9tabolisme, Clinique de P\u00e9diatrie, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Ladsous","sequence":"additional","affiliation":[{"name":"6H\u00f4pital Jean Bernard, Service d\u2019Endocrinologie-Diab\u00e9tologie, Venciennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Defoort-Dhellemmes","sequence":"additional","affiliation":[{"name":"3CHU de Lille, Exploration de la Vision et Neuro-Ophtalmologie, Lille, France"},{"name":"4Universit\u00e9 de Lille, Facult\u00e9 de M\u00e9decine, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gorwood","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Braud","sequence":"additional","affiliation":[{"name":"7Inserm U955, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Motterlini","sequence":"additional","affiliation":[{"name":"7Inserm U955, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Vatier","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"},{"name":"8Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Saint Antoine, Centre National de R\u00e9f\u00e9rence des Pathologies Rares de l\u2019Insulino-S\u00e9cr\u00e9tion et de l\u2019Insulino-Sensibilit\u00e9 (PRISIS), Service de Diab\u00e9tologie et Endocrinologie de la Reproduction, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lascols","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"},{"name":"9Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Saint Antoine, Laboratoire commun de Biologie et G\u00e9n\u00e9tique Mol\u00e9culaires, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Renard","sequence":"additional","affiliation":[{"name":"2CHU de Montpellier, H\u00f4pital Lapeyronie, Service d\u2019Endocrinologie-Diab\u00e9tologie-Nutrition, and Institut de G\u00e9nomique Fonctionnelle, CNRS, INSERM, Universit\u00e9 de Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Vigouroux","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"},{"name":"8Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Saint Antoine, Centre National de R\u00e9f\u00e9rence des Pathologies Rares de l\u2019Insulino-S\u00e9cr\u00e9tion et de l\u2019Insulino-Sensibilit\u00e9 (PRISIS), Service de Diab\u00e9tologie et Endocrinologie de la Reproduction, Paris, France"},{"name":"9Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Saint Antoine, Laboratoire commun de Biologie et G\u00e9n\u00e9tique Mol\u00e9culaires, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"J\u00e9ru","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France"},{"name":"9Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Saint Antoine, Laboratoire commun de Biologie et G\u00e9n\u00e9tique Mol\u00e9culaires, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of 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