Bariatric surgery in adolescents with severe obesity: Review and state of the art in France.

Severe obesity (body mass index>120% of BMI IOTF-30 cut off) and morbid obesity (BMI>140% of BMI IOTF-30 cut off) affect 5 to 10% of obese adolescents in France. Organic complications can be found in about 50% of these patients, and depressive symptoms in one-third of them. Finally, over 70% will suffer from adult morbid obesity associated with a marked increase in morbidity and mortality. However, the reversion of obesity strongly decreases, and may even cancels, these risks. In controlled randomized studies, lifestyle interventions have limited effectiveness on BMI in children (and none in adolescents). Bariatric surgery has been shown to have short-term effectiveness in adolescents with severe and morbid obesity: the average BMI loss after gastric banding was 11.6kg/m2 (95% confidence interval from 9.8 to 13.4), 16.6kg/m2 (95% confidence interval from 13.4 to 19.8) after bypass, and 14.1kg/m2 (95% confidence interval 10.8 to 17.5) after sleeve gastrectomy. The resolution of comorbidities was the main aim, as well as the improvement of quality of life. This is not a simple surgical intervention, and minor side effects have been reported in approximately 10-15% of teenagers who underwent surgery (more common with the gastric band), and severe side effects in nearly 1-5% (mainly with bypass). In France, recommendations regarding indications, the care pathway, multidisciplinary meetings, reference management structures and postoperative care have been published by the French National Health Authority (HAS) in 2016 to provide a framework for bariatric surgery in underage patients.

In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor.

BACKGROUND: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p'-DDT exposure and reproductive abnormalities. OBJECTIVES: To investigate the putative effects of p,p'-DDT on the human follitropin receptor (FSHR) function. METHODS AND RESULTS: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p'-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 µM p,p'-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 µM p,p'-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p'-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p'-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p'-DDT was dependent on the FSHR. In addition, p,p'-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p'-DDT and potentiation of the FSHR response to FSH by p,p'-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p'-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p'-DDT and 16a into the FSHR transmembrane bundle. CONCLUSION: p,p'-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptors. CITATION: Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016. In vitro effects of the endocrine disruptor p,p'-DDT on human follitropin receptor. Environ Health Perspect 124:991-999; http://dx.doi.org/10.1289/ehp.1510006.

Birth Weight Is Associated With the IGF-1 Response to GH in Children: Programming of the Anabolic Action of GH?

CONTEXT: Intrauterine programming of the somatotropic axis has been hypothesized in cases of intrauterine growth retardation. OBJECTIVE: The objective of the study was to study the effects of birth weight and body composition on GH sensitivity. DESIGN: This was a cross-sectional study with a single GH administration to assess GH sensitivity. SETTING: The study was conducted at the Department of Pediatric Endocrinology of an academic medical center. PATIENTS: One hundred normal short children aged from 4 to 17 years old (44 girls, 56 boys) separated into four groups: early childhood (aged 4-8 y, n = 14), late childhood (aged 9-12 y, pubertal stage 1, n = 30), early puberty (aged 10-15 y, stage 2, n = 32), and midpuberty (aged 12-17 y, stages 3 and 4, n = 24). INTERVENTION AND MAIN OUTCOME MEASURE: Serum IGF-1 at baseline and 24 hours after a single administration of GH (2 mg/m(2)) were measured. RESULTS: δIGF-1 significantly increased across the groups (P < .0001) with no gender difference, whereas the percentage of change in IGF-1 was similar (47% ± 32%). Independent predictors of δIGF-1 were birth weight SD score, fat percentage, fasting insulin (all positive predictors), and free fatty acids (negative predictor), with age, puberty, and baseline IGF-1 as adjusting variables (multiple R = 0.73, P < .0001). Independent predictors of the percentage of change in IGF-1 were birth weight SD score, fat percentage, and baseline IGF-1 (multiple R = 0.43, P < .001). CONCLUSION: This study suggests that in cases of low birth weight, intrauterine programming of GH sensitivity may be an adaptation to an expected poor postnatal nutritional environment, serving to restrict the anabolic action of GH. Conversely, postnatal excess energy stores may promote the anabolic action of GH.