Effect of Genotype and Previous GH Treatment on Adiposity in Adults With Prader-Willi Syndrome.
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/m2, 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/m2). 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.
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.
Muriel
M
Coupaye
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.
Maithé
M
Tauber
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.
Laurence
L
Cuisset
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.
Virginie
V
Laurier
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.
Eric
E
Bieth
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.
Jean-Marc
JM
Lacorte
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.
Jean-Michel
JM
Oppert
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.
Karine
K
Clément
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.
Christine
C
Poitou
D015502:Absorptiometry, Photon; D017667:Adipocytes; D050154:Adiposity; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D024182:Uniparental Disomy; D055815:Young Adult
D013006:Growth Hormone