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Le Touquet – Paris-Plage, France

Huvenne H.,GHICL | Huvenne H.,University Pierre and Marie Curie | Huvenne H.,Institute of Cardiometabolism and Nutrition ICAN | Dubern B.,University Pierre and Marie Curie | And 7 more authors.
Obesity Facts | Year: 2016

Obesity results from a synergistic relationship between genes and the environment. The phenotypic expression of genetic factors involved in obesity is variable, allowing to distinguish several clinical pictures of obesity. Monogenic obesity is described as rare and severe early-onset obesity with abnormal feeding behavior and endocrine disorders. This is mainly due to autosomal recessive mutations in genes of the leptin-melanocortin pathway which plays a key role in the hypothalamic control of food intake. Melanocortin 4 receptor(MC4R)-linked obesity is characterized by the variable severity of obesity and no notable additional phenotypes. Mutations in the MC4R gene are involved in 2-3% of obese children and adults; the majority of these are heterozygous. Syndromic obesity is associated with mental retardation, dysmorphic features, and organ-specific developmental abnormalities. Additional genes participating in the development of hypothalamus and central nervous system have been regularly identified. But to date, not all involved genes have been identified so far. New diagnostic tools, such as whole-exome sequencing, will probably help to identify other genes. Managing these patients is challenging. Indeed, specific treatments are available only for specific types of monogenic obesity, such as leptin deficiency. Data on bariatric surgery are limited and controversial. New molecules acting on the leptin-melanocortin pathway are currently being developed. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg. Source

Lloret-Linares C.,Assistance Publique Hopitaux de Paris | Lloret-Linares C.,University of Paris Descartes | Faucher P.,French Reference Center for Prader Willi Syndrome | Faucher P.,CEA DAM Ile-de-France | And 23 more authors.
International Journal of Obesity | Year: 2013

Context:The care of patients with hypothalamic obesity is challenging.Objective:To compare body composition, basal metabolic rate (BMR) and metabolic outcomes of adults, with lesional or genetic hypothalamic obesity, with obese patients suffering from primary obesity, once matched for body mass index (BMI).Design and patients:Adults with hypothalamic obesity of genetic origin (Prader Willi syndrome (PWS)) or acquired hypothalamic damage (HD), such as craniopharygioma, were compared with obese control candidates awaiting bariatric surgery (C), with a BMI between 35 and 65 kg m - 2, and aged between 18 and 50 years.Main outcome measures:Body composition measured by whole-body dual-energy X-ray absorptiometry scanning, BMR using indirect calorimetry, hormonal and metabolic assessments.Results:A total of 27 adults with a genetic diagnosis of PWS, 15 obese subjects with HD and 206 obese controls with similar BMI were studied. Compared with the control group, PWS patients had an increased percentage of fat mass (FM), and a decreased percentage of android FM. The BMR of PWS patients was significantly lower than controls and highly correlated with lean body mass in PWS and C patients. Body composition of HD was similar with those of obese patients. A trend toward an increased prevalence of diabetes in HD patients and of cytolysis in PWS was observed in comparison with primary obese patients.Conclusion:Genetic and lesional hypothalamic obesities have different consequences for phenotypic features such as body composition or BMR compared with primary obese patients. The mechanisms of adipose tissue development and metabolic complications may be different between genetic and lesional obesities. © 2013 Macmillan Publishers Limited. Source

Coupaye M.,Assistance Publique Hopitaux de Paris | Coupaye M.,Institute of Cardiology Metabolism and Nutrition | Coupaye M.,French Reference Center for Prader Willi Syndrome | Coupaye M.,University Paul Sabatier | And 44 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Children with Prader-Willi syndrome (PWS) who receive GH treatment have improved growth and body composition; however, data are lacking for adults when treatment is discontinued after completion of growth. Objectives: Our aim was to compare body composition and metabolic status in adults with PWS according to GH treatment in childhood and adolescence. Design: 64 adults (mean age: 25.4 years) with a genetic diagnosis of PWS were evaluated: 20 received GH in childhood (T), which had been discontinued at the time of this study, and 44 did not receive GH (C). Mean duration of treatment in the T group was 4.4 ± 2.7 years, age at baseline was 11.8 ± 2.7 years, mean time between the end of treatment and the current evaluation was 7.0 ± 4.4 years. Main Outcomes Measures: Dual-energy X-ray absorptiometry was used to assess body composition and fasting biological analyses evaluated metabolic status. Results (mean ± SD): Body mass index and percentage of fat mass were significantly lower in the T group (32.4 ± 10.3 vs 41.2 ± 11.1 kg/m2, P = 0.05 and 44.0 ± 9.6 vs 50.1 ± 7.2%, P = 0.02, respectively). Insulinemia and HOMA-IR in non-diabetic subjects were significantly lower in the T group (5.8 ± 5.9 vs 13.9 ± 11.6 μUI/ml, P = 0.03, and 1.6 ± 1.3 vs 2.7 ± 2.1, P = 0.04, respectively). Non-diabetic and diabetic subjects from the T group had a significantly lower HbA1c. Lipid profiles were similar between groups. Conclusions: GH treatment in childhood and adolescence is associated with significantly decreased bodymass index and improved body composition and metabolic status in adults with PWS at several years after discontinuing treatment. Copyright © 2013 by The Endocrine Society. Source

Lacroix D.,French Institute of Health and Medical Research | Lacroix D.,University Pierre and Marie Curie | Moutel S.,Institute of Cardiometabolism and Nutrition ICAN | Moutel S.,French Reference Center for Prader Willi Syndrome | And 22 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Prader-Willi syndrome (PWS), the most frequent syndrome of obesity, is a model of early fat mass (FM) development, but scarce data exist on adipose tissue characteristics. Objective: The objective of the study was to compare metabolic, fat distribution, and transcriptomic signatures of sc adipose tissue (scAT) in PWS adults, with matched obese adults with primary obesities. Main Outcomes and Measures: Hormonal and metabolic assessments, systemic inflammation, and geneexpression in scAT were compared between PWS patients and obese controls (OCs). Each 42nd PWS patient was matched with one randomly paired control with primary obesity. Matching factors were age, gender, fat mass (percentage), and diabetic status. Results: Compared with OCs, the PWS group had a decreased percentage of trunk FM and a better metabolic profile with decreased insulin and homeostasis model assessment, an index of insulin-resistance, and increased concentrations of serum adiponectin and ghrelin. Adipocyte size relative to body fat was significantly higher in PWS vs OCs. scAT in PWS patients was characterized by a transcriptomic functional signature with enrichment of themes related to immunoinflammation, the extracellular matrix, and angiogenesis. A RT-PCR targeted study revealed that candidate genes encoding proinflammatory markers and remodeling molecules, CD68, CD3e, IL-1β, chemokine (C-C motif) ligand 5, collagen type 4-α, and lysyl oxidase, were down-regulated. Conclusion: Matched for FM, PWS subjects have a better metabolic profile, a phenotype that could be linked to changes in scAT remodeling and promotion of adipocyte growth. Copyright © 2015 by the Endocrine Society. Source

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