Pediatric Obesity: Endocrinologic and Genetic Etiologies and Management
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OBESITY AND DIET (G. RAO, SECTION EDITOR)
Pediatric Obesity: Endocrinologic and Genetic Etiologies and Management Shashikala Gowda 1 & Tasa Seibert 1 & Naveen Uli 1 & Ryan Farrell 1
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Purpose of Review The prevalence of pediatric obesity has increased significantly over the past couple of generations. While monogenic obesity, syndromic obesity, and endocrinopathies associated with obesity have been increasingly recognized, they do not account for the increase in prevalence. We describe these rare conditions and the dysregulation of neuropathways in obesity and review successes and failures in treatments in both syndromic and nonsyndromic obesity. Recent Findings The best-described form of syndromic obesity is Prader–Willi Syndrome (PWS). While recent pharmacotherapies (specifically beloranib) demonstrated improvements in weight in PWS, the unfortunate adverse effect of deep vein thrombosis and pulmonary embolism necessitated the halting of its further development. Additional treatments are in development which target the signaling of ghrelin and other hypothalamic targets known to be dysregulated in PWS. For nonsyndromic obesity, lifestyle modifications remain the mainstay of treatment. However, recent large-scale interventions have had disappointing results. Bariatric surgery in children holds some promise, though complications and reoperations are common. Pharmacotherapies have been developed that treat rare monogenic forms of obesity, including MC4R agonists, which hold promise for these uncommon explanations for early childhood weight gain. There is evidence that methylation patterns in key genes in the neuroregulation of appetite are altered in individuals with obesity. Interestingly, this altered methylation is evident in sperm, which may have an impact on the heritability of gene expression across generations. Summary Pediatric obesity is complex and multifactorial. Efforts in rare monogenic and syndromic obesity may give rise to potential treatment opportunities in circumstances where lifestyle interventions are unsuccessful. Keywords Pediatrics . Obesity . Monogenic . Syndromic . Interventions . Therapeutics
Introduction This article is part of the Topical Collection on Obesity and Diet * Ryan Farrell [email protected] Shashikala Gowda [email protected] Tasa Seibert [email protected] Naveen Uli [email protected] 1
Division of Pediatric Endocrinology, Rainbow Babies and Children’s Hospital, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
The purpose of the review is to describe rare genetic syndromes and endocrinologic conditions associated with obesity in children. We also describe pathophysiologic mechanisms distorting energy balance in such conditions, a better understanding of which may lead to effective treatments.
Neuroregulation of Appetite and Genetic/Epigenetic Implications The regulation of energy balance is complex and under the influence of multiple
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