Cadoudal T, Buléon M, Sengenès C, Diene G, Desneulin F, Molinas C, Eddiry S, Conte-Auriol F, Daviaud D, Martin P G P, Bouloumié A, Salles J-P, Tauber M, Valet P
1] INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires I2MC, Toulouse, France [2] Université Paul Sabatier, UMR 1048, Toulouse, France.
Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologie médicale. Centre de référence du syndrome de Prader-Willi, Hôpital des enfants, Toulouse, France.
Int J Obes (Lond). 2014 Sep;38(9):1234-40. doi: 10.1038/ijo.2014.3. Epub 2014 Jan 10.
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.
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.
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.
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.
Herein, we report adipose tissue dysfunctions in children with PWS which may be partially restored by GH treatment.
普拉德-威利综合征（PWS）是由基因组印记过程异常导致下丘脑功能障碍，进而引起生长激素（GH）分泌改变所致。PWS与早期病态肥胖和身材矮小有关，而生长激素治疗可有效改善这些症状。
我们的目的是突出PWS患儿脂肪组织的结构和功能损伤，并研究生长激素治疗对这些参数的影响。
血浆样本和脂肪组织活检样本来自法国图卢兹PWS参考中心协调的23个研究中心。研究纳入了瘦素对照组（n = 33）、非综合征性肥胖组（n = 53）、未经治疗的PWS患儿（n = 26）和接受生长激素治疗的PWS患儿（n = 43）。在计划手术期间，从15名瘦素对照组、7名未经治疗的PWS患儿和8名接受生长激素治疗的PWS患儿身上获取脂肪组织活检样本。
与非综合征性肥胖儿童相比，PWS患儿的血糖、胰岛素水平和HOMA-IR降低，表明其胰岛素敏感性更高。相反，PWS患儿血浆中的炎症细胞因子如TNF-α、MCP-1和IL-8水平升高。与对照儿童相比，活检分析显示PWS患儿脂肪组织的基质血管部分祖细胞含量减少，且PWS脂肪细胞对β-肾上腺素能激动剂的脂解反应受损。有趣的是，生长激素治疗似乎改善了PWS患儿的这两种改变。
在此，我们报告了PWS患儿的脂肪组织功能障碍，生长激素治疗可能会部分恢复这些功能障碍。
