Vatier C

References (4)

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 : Use of Dipeptidyl Peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: a propensity score analysis from the CORONADO study - Roussel_2021_Diabetes.Obes.Metab__
Author(s) : Roussel R , Darmon P , Pichelin M , Goronflot T , Abouleka Y , Ait Bachir L , Allix I , Ancelle D , Barraud S , Bordier L , Carlier A , Chevalier N , Coffin-Boutreux C , Cosson E , Dorange A , Dupuy O , Fontaine P , Fremy B , Galtier F , Germain N , Guedj AM , Larger E , Laugier-Robiolle S , Laviolle B , Ludwig L , Monier A , Montanier N , Moulin P , Moura I , Prevost G , Reznik Y , Sabbah N , Saulnier PJ , Serusclat P , Vatier C , Wargny M , Hadjadj S , Gourdy P , Cariou B
Ref : Diabetes Obes Metab , : , 2021
Abstract : AIMS: Dipeptidyl Peptidase-4 (DPP-4), the target of oral antidiabetic drugs DDP-4 inhibitors, has been suggested to be involved in the pathogenesis of coronavirus infections, including COVID-19. It is unclear whether the routine use of DPP-4 inhibitors increases the severity of COVID-19 in people with type 2 diabetes (T2D). Our purpose was to investigate the association between routine use of DPP-4 inhibitors and the severity of COVID-19 infection in a large multicentric study. MATERIAL AND METHODS: This study was a secondary analysis of the CORONADO study on 2449 patients with T2D hospitalized for COVID-19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP-4 inhibitors users vs non-users) and were used into multivariable logistic regression models to estimate Average Treatment effect in the Treated as Inverse Probability of Treatment Weighting (IPTW). RESULTS: 596 participants were under DPP-4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non-users of DPP-4 inhibitors (27.7% vs 28.6%, P=0.68). In propensity analysis, the IPTW-adjusted models showed no significant association between use of DPP-4 inhibitors and the primary outcome within day 7 (OR [95%CI]: 0.95 [0.77-1.17]) or day 28 (OR [95%CI]: 0.96 [0.78-1.17]). Similar neutral findings were found between use of DPP-4 inhibitors and the risk of tracheal intubation and death. CONCLUSIONS: These data support the safety of DPP-4 inhibitors for diabetes management during the COVID-19 pandemic and they should not be discontinued. This article is protected by copyright. All rights reserved.
ESTHER : Roussel_2021_Diabetes.Obes.Metab__
PubMedSearch : Roussel_2021_Diabetes.Obes.Metab__
PubMedID: 33528920

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

Title : Diagnostic Challenge in PLIN1-Associated Familial Partial Lipodystrophy - Jeru_2019_J.Clin.Endocrinol.Metab_104_6025
Author(s) : Jeru I , Vantyghem MC , Bismuth E , Cervera P , Barraud S , Auclair M , Vatier C , Lascols O , Savage DB , Vigouroux C
Ref : J Clinical Endocrinology Metab , 104 :6025 , 2019
Abstract : CONTEXT: Heterozygous frameshift variants in PLIN1 encoding perilipin-1, a key protein for lipid droplet formation and triglyceride metabolism, have been implicated in familial partial lipodystrophy type 4 (FPLD4), a rare entity with only six families reported worldwide. The pathogenicity of other PLIN1 null variants identified in patients with diabetes and/or hyperinsulinemia was recently questioned because of the absence of lipodystrophy in these individuals and the elevated frequency of PLIN1 null variants in the general population. OBJECTIVES: To reevaluate the pathogenicity of PLIN1 frameshift variants owing to new data obtained in the largest series of patients with FPLD4. METHODS: We performed histological and molecular studies for patients referred to our French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity for lipodystrophy and/or insulin resistance and carrying PLIN1 frameshift variants. RESULTS: We identified two heterozygous PLIN1 frameshift variants segregating with the phenotype in nine patients from four unrelated families. The FPLD4 stereotypical signs included postpubertal partial lipoatrophy of variable severity, muscular hypertrophy, acromegaloid features, polycystic ovary syndrome and/or hirsutism, metabolic complications (e.g., hypertriglyceridemia, liver steatosis, insulin resistance, diabetes), and disorganized subcutaneous fat lobules with fibrosis and macrophage infiltration. CONCLUSIONS: These data suggest that some FPLD4-associated PLIN1 variants are deleterious. Thus, the evidence for the pathogenicity of each variant ought to be carefully considered before genetic counseling, especially given the importance of an early diagnosis for optimal disease management. Thus, we recommend detailed familial investigation, adipose tissue-focused examination, and follow-up of metabolic evolution.
ESTHER : Jeru_2019_J.Clin.Endocrinol.Metab_104_6025
PubMedSearch : Jeru_2019_J.Clin.Endocrinol.Metab_104_6025
PubMedID: 31504636