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LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells

التفاصيل البيبلوغرافية
العنوان: LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells
المؤلفون: Eric Renard, Corinne Vigouroux, Emilie Capel, Caroline Aguilhon, Roberto Motterlini, Camille Sollier, Claire Douillard, Isabelle Jéru, Laura Braud, Camille Vatier, Vasily Smirnov, Olivier Lascols, S. Defoort-Dhellemmes, Jennifer Gorwood, Martine Auclair, Miriam Ladsous
المساهمون: Vigouroux, Corinne, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département Endocrinologie-Diabétologie-Nutrition [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d’Exploration de la Vision et Neuro-ophtalmologie [CHU Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Faculté de Médecine Henri Warembourg - Université de Lille, Service Endocrinologie, diabétologie, maladies métaboliques et nutrition (LILLE - Endocrino), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Référence des Maladies Héréditaires du Métabolisme [Lille], Hôpital Jeanne de Flandre [Lille]-Clinique de Pédiatrie (Gastro-entérologie, hépatologie et nutrition)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CH de Valenciennes, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de Référence des Pathologies Rares de l'Insulino-Sécrétion et de l'Insulino-Sensibilité [CHu Saint-Antoine] (PRISIS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université Lille 2 - Faculté de Médecine, Service Endocrinologie Diabétologie et Métabolisme (LILLE - Endocrino), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
المصدر: European Journal of Endocrinology
European Journal of Endocrinology, 2021, 184 (1), pp.155-168. ⟨10.1530/EJE-20-1013⟩
European Journal of Endocrinology, BioScientifica, 2021, 184 (1), pp.155-168. ⟨10.1530/EJE-20-1013⟩
بيانات النشر: HAL CCSD, 2021.
سنة النشر: 2021
مصطلحات موضوعية: medicine.medical_specialty, Lipodystrophy, Endocrinology, Diabetes and Metabolism, Lipomatosis, Adipose tissue, 030209 endocrinology & metabolism, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Insulin resistance, Adipocyte, Internal medicine, Diabetes mellitus, Adipocytes, Humans, Medicine, Lipoatrophy, Alleles, Aged, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Models, Genetic, business.industry, Stem Cells, Partial Lipodystrophy, Genetic Variation, Cell Differentiation, Syndrome, General Medicine, Middle Aged, Sterol Esterase, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Phenotype, Adipose Tissue, chemistry, 030220 oncology & carcinogenesis, Lipomatosis, Multiple Symmetrical, Female, business
الوصف: Objective 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 LIPE encoding hormone-sensitive lipase (HSL), a key lipolytic enzyme, were implicated in three families worldwide. We aimed to further delineate LIPE-related clinical features and pathophysiological determinants. Methods 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. Results We identified new biallelic LIPE 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. LIPE-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction. Conslusions Biallelic LIPE 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.
وصف الملف: application/pdf
اللغة: English
تدمد: 0804-4643
1479-683X
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::72c6e47cec24ed926f7e1698e471be32Test
https://www.hal.inserm.fr/inserm-03138972Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....72c6e47cec24ed926f7e1698e471be32
قاعدة البيانات: OpenAIRE
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