T Cadoudal1, M Buléon1, C Sengenès1, G Diene2, F Desneulin3, C Molinas4, S Eddiry5, F Conte-Auriol6, D Daviaud1, P G P Martin7, A Bouloumié1, J-P Salles8, M Tauber9, P Valet1. 1. 1] INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires I2MC, Toulouse, France [2] Université Paul Sabatier, UMR 1048, Toulouse, France. 2. Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologie médicale. Centre de référence du syndrome de Prader-Willi, Hôpital des enfants, Toulouse, France. 3. Axe pédiatrique du CIC 9302/INSERM. Hôpital des enfants, Toulouse, France. 4. 1] Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologie médicale. Centre de référence du syndrome de Prader-Willi, Hôpital des enfants, Toulouse, France [2] Axe pédiatrique du CIC 9302/INSERM. Hôpital des enfants, Toulouse, France. 5. INSERM, UMR 1043, Toulouse, France. 6. 1] Axe pédiatrique du CIC 9302/INSERM. Hôpital des enfants, Toulouse, France [2] INSERM, UMR 1043, Toulouse, France. 7. 1] INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, Toulouse, France [2] Université de Toulouse, INP, UMR1331, Toxalim, Toulouse, France. 8. 1] Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologie médicale. Centre de référence du syndrome de Prader-Willi, Hôpital des enfants, Toulouse, France [2] Axe pédiatrique du CIC 9302/INSERM. Hôpital des enfants, Toulouse, France [3] INSERM, UMR 1043, Toulouse, France. 9. 1] Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologie médicale. Centre de référence du syndrome de Prader-Willi, Hôpital des enfants, Toulouse, France [2] INSERM, UMR 1043, Toulouse, France.
Abstract
BACKGROUND: Prader-Willi syndrome (PWS) results from abnormalities in the genomic imprinting process leading to hypothalamic dysfunction with an alteration of growth hormone (GH) secretion. PWS is associated with early morbid obesity and short stature which can be efficiently improved with GH treatment. OBJECTIVES: Our aims were to highlight adipose tissue structural and functional impairments in children with PWS and to study the modifications of those parameters on GH treatment. SUBJECTS AND METHODS: Plasma samples and adipose tissue biopsies were obtained from 23 research centers in France coordinated by the reference center for PWS in Toulouse, France. Lean controls (n=33), non-syndromic obese (n=53), untreated (n=26) and GH-treated PWS (n=43) children were enrolled in the study. Adipose tissue biopsies were obtained during scheduled surgeries from 15 lean control, 7 untreated and 8 GH-treated PWS children. RESULTS: Children with PWS displayed higher insulin sensitivity as shown by reduced glycemia, insulinemia and HOMA-IR compared with non-syndromic obese children. In contrast, plasma inflammatory cytokines such as TNF-α, MCP-1 and IL-8 were increased in PWS. Analysis of biopsies compared with control children revealed decreased progenitor cell content in the stromal vascular fraction of adipose tissue and an impairment of lipolytic response to β-adrenergic agonist in PWS adipocytes. Interestingly, both of these alterations in PWS seem to be ameliorated on GH treatment. CONCLUSION: Herein, we report adipose tissue dysfunctions in children with PWS which may be partially restored by GH treatment.
BACKGROUND:Prader-Willi syndrome (PWS) results from abnormalities in the genomic imprinting process leading to hypothalamic dysfunction with an alteration of growth hormone (GH) secretion. PWS is associated with early morbid obesity and short stature which can be efficiently improved with GH treatment. OBJECTIVES: Our aims were to highlight adipose tissue structural and functional impairments in children with PWS and to study the modifications of those parameters on GH treatment. SUBJECTS AND METHODS: Plasma samples and adipose tissue biopsies were obtained from 23 research centers in France coordinated by the reference center for PWS in Toulouse, France. Lean controls (n=33), non-syndromic obese (n=53), untreated (n=26) and GH-treated PWS (n=43) children were enrolled in the study. Adipose tissue biopsies were obtained during scheduled surgeries from 15 lean control, 7 untreated and 8 GH-treated PWSchildren. RESULTS:Children with PWS displayed higher insulin sensitivity as shown by reduced glycemia, insulinemia and HOMA-IR compared with non-syndromic obesechildren. In contrast, plasma inflammatory cytokines such as TNF-α, MCP-1 and IL-8 were increased in PWS. Analysis of biopsies compared with control children revealed decreased progenitor cell content in the stromal vascular fraction of adipose tissue and an impairment of lipolytic response to β-adrenergic agonist in PWS adipocytes. Interestingly, both of these alterations in PWS seem to be ameliorated on GH treatment. CONCLUSION: Herein, we report adipose tissue dysfunctions in children with PWS which may be partially restored by GH treatment.
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