Growth hormone induced lipolysis during short- and long-term administration in adult Prader–Willi patients

Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Solna, 17176 Stockholm, Sweden.
Growth Hormone & IGF Research (Impact Factor: 1.41). 01/2006; 15(6):411-5. DOI: 10.1016/j.ghir.2005.08.005
Source: PubMed


Prader-Willi syndrome (PWS) is a complex genetic disease, clinically characterised by short stature, abnormal body composition, with more body fat than lean body mass, hyperphagia and obesity. Partial growth hormone (GH) deficiency is common, and GH treatment to PWS children and adults has shown beneficial effects on body composition. In this study, we have evaluated indices of GH's lipolytic effect in 6 PWS adults analysing glycerol, lactate and glucose in dialysate from microdialysis in subcutaneous abdominal adipose tissue. The patients were four men and two women, 19-37 years old; all hypogonadal. BMI was 24.2-49.1, mean 35.9 kg/m(2). All had normal serum insulin levels. They received GH therapy (Genotropin Pfizer) during 12 months and doses were individually titrated to normal serum IGF-I for age. Immediately before treatment start and at 12 months, 30-36 h after the last GH injection, sampling of dialysate was carried out at night (11 p.m. to 7 a.m.), as well as after intravenously injection of a standardised GH dose (0.8 mg). At baseline individual mean night time glycerol and lactate were similar to levels in adults without PWS (160.7-278.1 micromol/L and 0.80-3.99 mmol/L, respectively), and did not change with 12 months GH treatment. Glucose levels were normal, except in a patient with diabetes, and did not change during the study. Compared to baseline the immediate effect of GH injection resulted in a significant increase in glycerol levels after 12 months. In conclusion, night time lipolytic response in this small group of PWS adults seemed normal and did not change after 12 months GH treatment. On the other hand short-term GH induced lipolysis increased, indicating normal lipolytic response in PWS.

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    ABSTRACT: Prader-Willi syndrome (PWS) is associated with GH deficiency, deleterious changes in body composition and function. As the effects of recombinant human GH (rhGH) in PWS adults have not been well established, we sought to conduct a meta-analysis of pertinent studies. Meta-analysis of studies examining the effects of rhGH therapy in PWS adults. One hundred and thirty four PWS adults (75 men, 59 women). Literature searches, including publications (PubMed, EMBASE and the Cochrane Register), and abstracts presented at meetings through July 2011 describing studies of rhGH therapy in PWS adults; 8/1194 articles, describing unique cohorts, were included. Two authors independently extracted data and examined study quality. rhGH therapy for 12 months led to [weighted mean difference (95% CI)] decreased body fat [-2·91% (-3·90, -1·91)], visceral [-32·97 cm(2) (-55·67, -10·26)] and subcutaneous adiposity [-55·24 cm(2) (-89·05, -21·44)], and increased lean body mass (LBM) [2·41 Kg (1·32, 3·49)]. Similar changes in body fat [-2·89% (-4·69, -1·07)] and LBM [2·82 Kg (1·31, 4·33)] were found in longer studies. There were no changes in body mass index (BMI) or lipids. There was a small increase in fasting glucose [0·27 mmol/l (0·05, 0·49)] and trends towards higher fasting insulin [20·24 pmol/l (-0·55, 41·02)] and insulin resistance [HOMA: 0·60 (-0·04, 1·24)] after rhGH therapy for 12 months. In PWS adults, rhGH therapy led to decreased body adiposity and increased LBM without changes in BMI or lipids. There was a small increase in fasting glucose and trends towards higher insulin and insulin resistance.
    Clinical Endocrinology 11/2011; 77(1):86-93. DOI:10.1111/j.1365-2265.2011.04303.x · 3.46 Impact Factor
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    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 glycaemia, 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 to 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.International Journal of Obesity accepted article preview online, 10 January 2014. doi:10.1038/ijo.2014.3.
    International journal of obesity (2005) 01/2014; 38(9). DOI:10.1038/ijo.2014.3 · 5.00 Impact Factor

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