Insulin response dysregulation explains ...
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Article dans une revue scientifique: Article original
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Title :
Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome
Author(s) :
Limoge, F. [Auteur]
Génétique des Anomalies du Développement [GAD]
Faivre, L. [Auteur]
Génétique des Anomalies du Développement [GAD]
Gautier, T. [Auteur]
Lipides - Nutrition - Cancer (U866) [LNC]
Petit, J. M. [Auteur]
Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon)
Gautier, E. [Auteur]
FHU TRANSLAD (CHU de Dijon)
Masson, D. [Auteur]
Jego, G. [Auteur]
El Chehadeh-Djebbar, S. [Auteur]
Marle, N. [Auteur]
Carmignac, V. [Auteur]
Deckert, V. [Auteur]
Brindisi, M. C. [Auteur]
Edery, P. [Auteur]
Hôpital Femme Mère Enfant [CHU - HCL] [HFME]
Ghoumid, Jamal [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Blair, E. [Auteur]
Churchill Hospital Oxford Centre for Haematology
Lagrost, L. [Auteur]
Lipides - Nutrition - Cancer (U866) [LNC]
Thauvin-Robinet, C. [Auteur]
Génétique des Anomalies du Développement [GAD]
Duplomb, L. [Auteur]
Génétique des Anomalies du Développement [GAD]
Génétique des Anomalies du Développement [GAD]
Faivre, L. [Auteur]
Génétique des Anomalies du Développement [GAD]
Gautier, T. [Auteur]
Lipides - Nutrition - Cancer (U866) [LNC]
Petit, J. M. [Auteur]
Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon)
Gautier, E. [Auteur]
FHU TRANSLAD (CHU de Dijon)
Masson, D. [Auteur]
Jego, G. [Auteur]
El Chehadeh-Djebbar, S. [Auteur]
Marle, N. [Auteur]
Carmignac, V. [Auteur]
Deckert, V. [Auteur]
Brindisi, M. C. [Auteur]
Edery, P. [Auteur]
Hôpital Femme Mère Enfant [CHU - HCL] [HFME]
Ghoumid, Jamal [Auteur]

Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Blair, E. [Auteur]
Churchill Hospital Oxford Centre for Haematology
Lagrost, L. [Auteur]
Lipides - Nutrition - Cancer (U866) [LNC]
Thauvin-Robinet, C. [Auteur]
Génétique des Anomalies du Développement [GAD]
Duplomb, L. [Auteur]
Génétique des Anomalies du Développement [GAD]
Journal title :
Human Molecular Genetics
Abbreviated title :
Hum. Mol. Genet.
Volume number :
24
Pages :
6603–6613
Publisher :
Oxford Academic
Publication date :
2015-12-01
ISSN :
0964-6906
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Cohen Syndrome (CS) is a rare autosomal recessive disorder, with defective glycosylation secondary to mutations in the VPS13B gene, which encodes a protein of the Golgi apparatus. Besides congenital neutropenia, retinopathy ...
Show more >Cohen Syndrome (CS) is a rare autosomal recessive disorder, with defective glycosylation secondary to mutations in the VPS13B gene, which encodes a protein of the Golgi apparatus. Besides congenital neutropenia, retinopathy and intellectual deficiency, CS patients are faced with truncal obesity. Metabolism investigations showed abnormal glucose tolerance tests and low HDL values in some patients, and these could be risk factors for the development of diabetes mellitus and/or cardiovascular complications. To understand the mechanisms involved in CS fat storage, we used two models of adipogenesis differentiation: (i) SGBS pre-adipocytes with VPS13B invalidation thanks to siRNA delivery and (ii) CS primary fibroblasts. In both models, VPS13B invalidation led to accelerated differentiation into fat cells, which was confirmed by the earlier and increased expression of specific adipogenic genes, consequent to the increased response of cells to insulin stimulation. At the end of the differentiation protocol, these fat cells exhibited decreased AKT2 phosphorylation after insulin stimulation, which suggests insulin resistance. This study, in association with the in-depth analysis of the metabolic status of the patients, thus allowed us to recommend appropriate nutritional education to prevent the occurrence of diabetes mellitus and to put forward recommendations for the follow-up of CS patients, in particular with regard to the development of metabolic syndrome. We also suggest replacing the term obesity by abnormal fat distribution in CS, which should reduce the number of inappropriate diagnoses in patients who are referred only on the basis of intellectual deficiency associated with obesity.Show less >
Show more >Cohen Syndrome (CS) is a rare autosomal recessive disorder, with defective glycosylation secondary to mutations in the VPS13B gene, which encodes a protein of the Golgi apparatus. Besides congenital neutropenia, retinopathy and intellectual deficiency, CS patients are faced with truncal obesity. Metabolism investigations showed abnormal glucose tolerance tests and low HDL values in some patients, and these could be risk factors for the development of diabetes mellitus and/or cardiovascular complications. To understand the mechanisms involved in CS fat storage, we used two models of adipogenesis differentiation: (i) SGBS pre-adipocytes with VPS13B invalidation thanks to siRNA delivery and (ii) CS primary fibroblasts. In both models, VPS13B invalidation led to accelerated differentiation into fat cells, which was confirmed by the earlier and increased expression of specific adipogenic genes, consequent to the increased response of cells to insulin stimulation. At the end of the differentiation protocol, these fat cells exhibited decreased AKT2 phosphorylation after insulin stimulation, which suggests insulin resistance. This study, in association with the in-depth analysis of the metabolic status of the patients, thus allowed us to recommend appropriate nutritional education to prevent the occurrence of diabetes mellitus and to put forward recommendations for the follow-up of CS patients, in particular with regard to the development of metabolic syndrome. We also suggest replacing the term obesity by abnormal fat distribution in CS, which should reduce the number of inappropriate diagnoses in patients who are referred only on the basis of intellectual deficiency associated with obesity.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Submission date :
2023-06-05T07:52:08Z
2023-10-19T10:27:10Z
2023-10-19T10:27:10Z