Coupaye Muriel, Tauber Maithé, Cuisset Laurence, Laurier Virginie, Bieth Eric, Lacorte Jean-Marc, Oppert Jean-Michel, Clément Karine, Poitou Christine
Assistance Publique-Hôpitaux de Paris (M.C., J.-M.O., K.C., C.P.), Pitié-Salpêtrière Hospital, Nutrition Department, French Reference Centre for Prader-Willi Syndrome, and Institute of Cardiometabolism and Nutrition (J.-M.O., K.C., C.P.), Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche 1166, Nutriomic Team Pitié-Salpêtrière Hospital, Paris F-75013, France; Department of Endocrinology, Bone Diseases, Genetics, and Gynaecology (M.T.), Children's Hospital, French Reference Centre for Prader-Willi Syndrome, Toulouse F-31059 France and Université Paul Sabatier, Toulouse III F-31062, France; Inserm (M.T.), 1043 Team 12, Human Physiopathology Centre, and Department of Medical Genetics (E.B.), Purpan Hospital, Toulouse F-31059, France; Assistance Publique-Hôpitaux de Paris (L.C.), Laboratory of Biochemistry and Molecular Genetics, Institut Cochin and Cochin Hospital, Université Paris Descartes, Paris F-75014, France; Assistance Publique-Hôpitaux de Paris (V.L.), French Reference Center for Prader-Willi Syndrome, Hôpital Marin d'Hendaye, Hendaye F-64701, France; and Assistance Publique-Hôpitaux de Paris (J.-M.L.), Pitié-Salpêtrière Hospital, Department of Endocrine and Oncology Biochemistry, Paris F-75013 France.
J Clin Endocrinol Metab. 2016 Dec;101(12):4895-4903. doi: 10.1210/jc.2016-2163. Epub 2016 Sep 23.
Adults with Prader-Willi syndrome (PWS) have an increased proportion of sc fat mass compared with body mass index (BMI)-matched controls, but whether the genotype influences body composition and metabolic profile remains controversial.
To assess body composition and metabolic features in adults with PWS, according to genetic subtype. In addition, the effect of previous GH treatment was assessed. Main Outcomes and Measures: Body composition (Dual Energy X-ray Absorptiometry) and metabolic parameters were compared in PWS adults (mean age, 25.5 ± 8.9 y) with deletion (n = 47) or uniparental disomy (UPD) (n = 26), taking into account GH treatment in childhood and/or adolescence. In subgroups, adipocyte size, fasting total ghrelin levels, and resting energy expenditure were measured, and hyperphagia was assessed by the Dykens Hyperphagia Questionnaire.
Body composition (Dual Energy X-ray Absorptiometry) and metabolic parameters were compared in PWS adults (mean age, 25.5 ± 8.9 y) with deletion (n = 47) or uniparental disomy (UPD) (n = 26), taking into account GH treatment in childhood and/or adolescence. In subgroups, adipocyte size, fasting total ghrelin levels, and resting energy expenditure were measured, and hyperphagia was assessed by the Dykens Hyperphagia Questionnaire.
In the whole sample, the deletion group had a higher BMI compared with UPD (40.9 ± 11.5 vs 34.6 ± 9.6 kg/m, P = .02), but there was no difference between groups in percent body fat, metabolic profile, adipocyte size, resting energy expenditure, hyperphagia score, or ghrelin levels. In subjects previously treated with GH, BMI was not different between UPD and deletion groups (33.0 ± 9.7 vs 33.5 ± 11.1 kg/m). In addition, previous GH treatment was associated with decreased percent body fat and adipocyte volume only in the deletion group.
A deletion genotype in adults with PWS is associated with increased BMI. GH treatment in childhood and/or adolescence limits this deleterious phenotypic effect with improved adiposity markers. This study suggests relationships between the molecular phenotype of PWS and adipose tissue development as well as sensitivity to GH.
与体重指数（BMI）匹配的对照组相比，普拉德-威利综合征（PWS）成年患者的皮下脂肪量占比更高，但基因型是否会影响身体组成和代谢特征仍存在争议。
根据基因亚型评估PWS成年患者的身体组成和代谢特征。此外，评估既往生长激素（GH）治疗的效果。主要结局指标：采用双能X线吸收法比较PWS成年患者（平均年龄25.5±8.9岁）中缺失型（n = 47）和单亲二体型（UPD）（n = 26）的身体组成和代谢参数，同时考虑儿童期和/或青春期的GH治疗情况。在亚组中，测量脂肪细胞大小、空腹总胃饥饿素水平和静息能量消耗，并通过戴肯斯贪食问卷评估贪食情况。
采用双能X线吸收法比较PWS成年患者（平均年龄25.5±8.9岁）中缺失型（n = 47）和单亲二体型（UPD）（n = 26）的身体组成和代谢参数，同时考虑儿童期和/或青春期的GH治疗情况。在亚组中，测量脂肪细胞大小、空腹总胃饥饿素水平和静息能量消耗，并通过戴肯斯贪食问卷评估贪食情况。
在整个样本中，缺失组的BMI高于UPD组（40.9±11.5 vs 34.6±9.6 kg/m²，P = 0.02），但两组在体脂百分比、代谢特征、脂肪细胞大小、静息能量消耗、贪食评分或胃饥饿素水平方面无差异。在既往接受过GH治疗的患者中，UPD组和缺失组的BMI无差异（33.0±9.7 vs 33.5±11.1 kg/m²）。此外，既往GH治疗仅在缺失组中与体脂百分比降低和脂肪细胞体积减小有关。
PWS成年患者中的缺失基因型与BMI升高有关。儿童期和/或青春期的GH治疗通过改善肥胖标志物来限制这种有害的表型效应。本研究提示了PWS的分子表型与脂肪组织发育以及对GH敏感性之间的关系。
