Impairment of adipose tissue in Prader–Willi syndrome rescued by growth hormone treatment

• Published in: International Journal of Obesity Vol. 38; no. 9; pp. 1234 - 1240
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2014; Nature Publishing Group
• Subjects: 692/699/2743/393; 692/700/565/238; Abnormalities; Adipocytes; Adipocytes - metabolism; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose tissues; Adolescent; Biological and medical sciences; Biopsy; Blood glucose; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Composition; Body fat; Body Height - drug effects; Body mass index; Care and treatment; Cells (biology); Child; Child, Preschool; Children; Children & youth; Complex syndromes; Cytokines; Dosage and administration; Epidemiology; Female; France; Genetic disorders; Genomic imprinting; Growth hormones; Health Promotion and Disease Prevention; Hormone Replacement Therapy; Human Growth Hormone - therapeutic use; Humans; Hypothalamus; Impairment; Infant; Inflammation; Insulin; Interleukin 8; Internal Medicine; Life Sciences; Lipolysis; Male; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Monocyte chemoattractant protein 1; Obesity; Obesity in children; Obesity, Morbid - drug therapy; Obesity, Morbid - etiology; Obesity, Morbid - metabolism; original-article; Parameter modification; Patient outcomes; Pediatric Obesity - drug therapy; Pediatric Obesity - etiology; Pediatric Obesity - metabolism; Physical growth; Physiological aspects; Plasma; Prader-Willi syndrome; Prader-Willi Syndrome - complications; Prader-Willi Syndrome - drug therapy; Prader-Willi Syndrome - metabolism; Progenitor cells; Public Health; Research facilities; Somatotropin; Stem cells; Structure-function relationships; Sympathomimetics; Treatment Outcome; Tumor necrosis factor-α; Young Adult; France; Europe; adipose tissue; progenitor cells; Prader–Willi syndrome; lipolysis; Endocrinopathy; Obesity; Adipose tissue; Nutrition; Stem cell; Diseases of the osteoarticular system; Nutrition disorder; Metabolic diseases; Lipolysis; Genetic disease; Somatotropin; Treatment; Adenohypophyseal hormone; Prader―Willi syndrome; Complex syndrome; Prader Labhart Willi syndrome; Nutritional status; Prader-Willi syndrome; BIRTH INCIDENCE; ADULTS; IMPROVES BODY-COMPOSITION; TERM; PREVALENCE; CHILDHOOD; OBESITY; INSULIN-RESISTANCE; FAT
• ISSN: 0307-0565; 1476-5497; 1476-5497; 0307-0565
• DOI: 10.1038/ijo.2014.3

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.