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      Weight Loss after Bariatric Surgery in Morbidly Obese Adolescents with MC4R mutations

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          Abstract

          Objective

          To determine the frequency of Melanocortin4 Receptor ( MC4R) mutations in morbidly obese adolescents undergoing bariatric surgery and compare weight loss outcomes in patients with and without mutations.

          Design and Methods

          In this prospective cohort study, 135 adolescent patients evaluated for bariatric surgery were screened for MC4R mutations; 56 had 12 month postoperative data available for analysis.

          Results

          MC4R mutations were detected in five of the 135 patients (3.7%); four underwent restrictive bariatric surgery. For the three patients with gastric banding, percent excess weight loss (%EWL) postoperatively was 36.0% at 5 years in one, 47% at 4 years in the second, and 85% at 1 year in the third. For the patient with gastric sleeve resection, %EWL of 96% was attained at 1 year postoperatively. The four MC4R cases had a higher, although non-significant, %EWL compared to 52 non-matched controls at 12 months postoperatively (48.6% vs. 23.4%; p<0.37). When matched by age, sex, and race to 14 controls, there was no significant difference in %EWL (p < 0.31), BMI change (p< 0.27), or absolute weight loss (p <0.20).

          Conclusion

          The frequency of MC4R mutations is similar to prior studies, with affected patients showing beneficial weight loss outcomes.

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          Most cited references30

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          NIH conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel.

          Surgeons, gastroenterologists, endocrinologists, psychiatrists, nutritionists, and other health care professionals, as well as members of the public convened to address nonsurgical treatments for severe obesity, surgical treatments for severe obesity, and criteria for selection, the efficacy, and risks of surgical treatments for severe obesity, and the need for future research on and epidemiologic evaluation of these therapies. The National Institutes of Health Consensus Development Panel recommended that patients seeking therapy for severe obesity for the first time should be considered for treatment in a nonsurgical program that integrates a dietary regimen, appropriate exercise, behavior modification, and psychological support; that gastric restrictive or bypass procedures could be considered for well-informed and motivated patients in whom the operative risks were acceptable; that patients who are candidates for surgical procedures should be selected carefully after evaluation by a multidisciplinary team with medical, surgical, psychiatric, and nutritional expertise; that surgery be done by a surgeon who has substantial experience in the particular procedure and who works in a clinical setting with adequate support for all aspects of management and assessment; and that patients undergo lifelong medical surveillance after surgery.
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            Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain.

            POMC, the precursor of ACTH, MSH, and beta-endorphin peptides, is expressed in the pituitary and in two sites in the brain, in the arcuate nucleus of the hypothalamus and the commissural nucleus of the solitary tract of the brain stem. Little is known regarding the functions of melanocortin (ACTH and MSH) peptides in the brain. We report here the detailed neuroanatomical distribution of the MC4-R mRNA in the adult rat brain. The melanocortin 3 receptor (MC3-R), characterized previously, was found to be expressed in arcuate nucleus neurons and in a subset of their presumptive terminal fields but in few regions of the brainstem. The highly conserved MC4-R is much more widely expressed than MC3-R and is pharmacologically distinct. MC4-R mRNA was found in multiple sites in virtually every brain region, including the cortex, thalamus, hypothalamus, brainstem, and spinal cord. Unlike the MC3-R, MC4-R mRNA is found in both parvicellular and magnocellular neurons of the paraventricular nucleus of the hypothalamus, suggesting a role in the central control of pituitary function. MC4-R is also unique in its expression in numerous cortical and brainstem nuclei. Together, MC3-R and/or MC-4R mRNA are found in every nucleus reported to bind MSH in the adult rat brain and define neuronal circuitry known to be involved in the control of diverse neuroendocrine and autonomic functions. The high degree of conservation, distinct pharmacology, and unique neuronal distribution of the MC4 receptor suggest specific and complex roles for the melanocortin peptides in neuroendocrine and autonomic control.
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              Laparoscopic adjustable gastric banding in severely obese adolescents: a randomized trial.

              Adolescent obesity is a common and serious health problem affecting more than 5 million young people in the United States alone. Bariatric surgery is being evaluated as a possible treatment option. Laparoscopic adjustable gastric banding (gastric banding) has the potential to provide a safe and effective treatment. To compare the outcomes of gastric banding with an optimal lifestyle program on adolescent obesity. A prospective, randomized controlled trial of 50 adolescents between 14 and 18 years with a body mass index (BMI) higher than 35, recruited from the Melbourne, Australia, community, assigned either to a supervised lifestyle intervention or to undergo gastric banding, and followed up for 2 years. The study was performed between May 2005 and September 2008. Weight loss. Secondary outcomes included change in metabolic syndrome, insulin resistance, quality of life, and adverse outcomes. Twenty-four of 25 patients in the gastric banding group and 18 of 25 in lifestyle group completed the study. Twenty-one (84%) in the gastric banding and 3 (12%) in the lifestyle groups lost more than 50% of excess weight, corrected for age. Overall, the mean changes in the gastric banding group were a weight loss of 34.6 kg (95% CI, 30.2-39.0), representing an excess weight loss of 78.8% (95% CI, 66.6%-91.0%), 12.7 BMI units (95% CI, 11.3-14.2), and a BMI z score change from 2.39 (95% CI, 2.05-2.73) to 1.32 (95% CI, 0.98-1.66). The mean losses in the lifestyle group were 3.0 kg (95% CI, 2.1-8.1), representing excess weight loss of 13.2% (95% CI, 2.6%-21.0%), 1.3 BMI units (95% CI, 0.4-2.9), and a BMI z score change from 2.41 (95% CI, 2.21-2.66) to 2.26 (95% CI, 1.91-2.43). At entry, 9 participants (36%) in the gastric banding group and 10 (40%) in the lifestyle group had the metabolic syndrome. At 24 months, none of the gastric banding group had the metabolic syndrome (P = .008; McNemar chi(2)) compared with 4 of the 18 completers (22%) in the lifestyle group (P = .13). The gastric banding group experienced improved quality of life with no perioperative adverse events. However, 8 operations (33%) were required in 7 patients for revisional procedures either for proximal pouch dilatation or tubing injury during follow-up. Among obese adolescent participants, use of gastric banding compared with lifestyle intervention resulted in a greater percentage achieving a loss of 50% of excess weight, corrected for age. There were associated benefits to health and quality of life. ANZCTR Identifier: 12605000160639.
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                Author and article information

                Journal
                101264860
                32902
                Obesity (Silver Spring)
                Obesity (Silver Spring)
                Obesity (Silver Spring, Md.)
                1930-7381
                1930-739X
                13 September 2013
                15 October 2013
                January 2014
                01 July 2014
                : 22
                : 1
                : 225-231
                Affiliations
                [1 ]Department of Pediatrics, Division of Pediatric Endocrinology, Columbia University Medical Center, New York, NY, United States, 10032
                [2 ]Department of Pediatrics, Division of Molecular Genetics, Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, NY, United States, 10032
                [3 ]Division of Pediatric Surgery, Department of Surgery, Columbia University Medical Center, New York, NY, United States, 10032
                [4 ]Department of Medicine, Columbia University Medical Center, New York, NY, United States, 10032
                Author notes
                Address correspondence and reprint requests to: Ilene Fennoy, MD MPH, Columbia University Medical Center, 622 West 168th Street, PH 5E-522, New York, New York 10032, Telephone: (212) 305-6559, Fax: (212) 305-4778, if1@ 123456columbia.edu
                Article
                NIHMS484687
                10.1002/oby.20511
                3880391
                23740648
                994fae28-7526-4831-991a-59323b76813a
                History
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: T32 DK065522 || DK
                Categories
                Article

                Medicine
                mc4r,obesity,adolescents,bariatric surgery
                Medicine
                mc4r, obesity, adolescents, bariatric surgery

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