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.
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Acknowledgements
This study was funded by grants from the French ministry of health (Programme Hospitalier de Recherche Clinique) and from the Région Midi-Pyrénées. We thank the Anexplo platform for Luminex analyses and are deeply grateful to the children participating in this study, their families and medical staff who performed children recruitment, clinical data collection and tissue sampling. National Program for Clinical Research from the French government (grant 0811601) and Clinical Research Program of Midi-Pyrénées (grant 09004797).
AUTHOR CONTRIBUTIONS
GD, JPS, MT and PV designed the study and conceived experiments. FD, CM, SE and FCA performed data collection. TC, MB, CS and DD carried out experiments. TC, MB, CS, AB, PM analyzed and interpreted data. All authors were involved in writing the paper and had final approval of the submitted and published versions.
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Cadoudal, T., Buléon, M., Sengenès, C. et al. Impairment of adipose tissue in Prader–Willi syndrome rescued by growth hormone treatment. Int J Obes 38, 1234–1240 (2014). https://doi.org/10.1038/ijo.2014.3
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DOI: https://doi.org/10.1038/ijo.2014.3
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