Sollier C

References (2)

Title : LIPE-related lipodystrophic syndrome: clinical characteristics and disease modelling using adipose stem cells - Sollier_2020_Eur.J.Endocrinol_184_155
Author(s) : Sollier C , Capel E , Aguilhon C , Smirnov V , Auclair M , Douillard C , Ladsous M , Defoort-Dhellemmes S , Gorwood J , Braud L , Motterlini R , Vatier C , Lascols O , Renard E , Vigouroux C , Jeru I
Ref : European Journal of Endocrinology , 184 :155 , 2021
Abstract : 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 pseudolipomatous 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. Conclusions 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.
ESTHER : Sollier_2020_Eur.J.Endocrinol_184_155
PubMedSearch : Sollier_2020_Eur.J.Endocrinol_184_155
PubMedID: 33112291
Gene_locus related to this paper: human-LIPE

Title : Lipodystrophic syndromes: From diagnosis to treatment - Sollier_2020_Ann.Endocrinol.(Paris)_81_51
Author(s) : Sollier C , Vatier C , Capel E , Lascols O , Auclair M , Janmaat S , Feve B , Jeru I , Vigouroux C
Ref : Ann Endocrinol (Paris) , 81 :51 , 2020
Abstract : Lipodystrophic syndromes are acquired or genetic rare diseases, characterised by a generalised or partial lack of adipose tissue leading to metabolic alterations linked to strong insulin resistance. They encompass a variety of clinical entities due to primary defects in adipose differentiation, in the structure and/or regulation of the adipocyte lipid droplet, or due to immune-inflammatory aggressions, chromatin deregulations and/or mitochondrial dysfunctions affecting adipose tissue. Diagnosis is based on clinical examination, pathological context and comorbidities, and on results of metabolic investigations and genetic analyses, which together determine management and genetic counselling. Early lifestyle and dietary measures focusing on regular physical activity and avoiding excess energy intake are crucial. They are accompanied by multidisciplinary follow-up adapted to each clinical form. In case of hyperglycemia, antidiabetic medications, with metformin as a first-line therapy in adults, are used in addition to lifestyle and dietary modifications. When standard treatments have failed to control metabolic disorders, the orphan drug metreleptin, an analog of leptin, can be effective in certain forms of lipodystrophy syndrome. Metreleptin therapy indications, prescription and monitoring were recently defined in France, representing a major improvement in patient care.
ESTHER : Sollier_2020_Ann.Endocrinol.(Paris)_81_51
PubMedSearch : Sollier_2020_Ann.Endocrinol.(Paris)_81_51
PubMedID: 31982105