Childhood obesity

Abstract

Worldwide prevalence of childhood obesity has increased greatly during the past three decades. The increasing occurrence in children of disorders such as type 2 diabetes is believed to be a consequence of this obesity epidemic. Much progress has been made in understanding of the genetics and physiology of appetite control and from these advances, elucidation of the causes of some rare obesity syndromes. However, these rare disorders have so far taught us few lessons about prevention or reversal of obesity in most children. Calorie intake and activity recommendations need reassessment and improved quantification at a population level because of sedentary lifestyles of children nowadays. For individual treatment, currently recommended calorie prescriptions might be too conservative in view of evolving insight into the so-called energy gap. Although quality of research into both prevention and treatment has improved, high-quality multicentre trials with long-term follow-up are needed. Meanwhile, prevention and treatment approaches to increase energy expenditure and decrease intake should continue. Recent data suggest that the spiralling increase in childhood obesity prevalence might be abating; increased efforts should be made on all fronts to continue this potentially exciting trend.

Conflict of interest statement

Conflict of interest statement

Dr. Kimm serves as a member of the Medical Advisory Board of the Aspartame Resource Center, from which she received no support for her research or her effort in this manuscript.

Copyright 2010 Elsevier Ltd. All rights reserved.

Figures

Figure 1. A simplified model of the leptin signalling pathway

Since the discovery of leptin, understanding of the mechanisms that control energy balance has rapidly advanced. Unfortunately, except for leptin replacement therapy in a handful of leptin deficient individuals, there is yet to emerge any interventions that effectively prevent or treat obesity in the general population. Both insulin and leptin are secreted in proportion to body fatness and serve as adiposity signals, acting on the same neurons of the hypothalamic arcuate nucleus to regulate energy homeostasis. Ghrelin, which is secreted by the stomach and duodenum, serves as a hunger signal at the hypothalamus and brainstem, while other peptides secreted by the GI tract, including PYY, act as satiation signals. The ligands leptin, POMC, , CART, and BDNF,, the receptors for leptin, , melanocortins,– and BDNF, and the enzyme PC1, have been found to have function-altering mutations associated with obesity in children. Mutations in the ligands and receptors for NPY, AGRP, CPE,, and MCH have been found to alter energy balance in rodents, but have not been as convincingly shown to be associated with human obesity. Lines with arrowheads indicate stimulatory action. Lines ending with a perpendicular end-block indicate inhibitory action. Abbreviations: GI, gastrointestinal; PYY, peptide YY, IR, insulin receptor; LR, leptin receptor, NPY, neuropeptide Y; AGRP, agouti-related protein; POMC, pro-opiomelanocortin; CART, cocaine-amphetamine related transcript; PC1, prohormone convertase 1; CPE, carboxypeptidase E; MSH, melanocyte stimulating hormone; TRH, thyrotropin-releasing hormone; MCH, melanin concentrating hormone; GABA, gamma amino butyric acid; BDNF, brain-derived neurotrophic factor; TrkB, tyrosine kinase receptor B.

Figure 2. Recommended evaluation of childhood-onset obesity

The clinical history and examination of the patient should guide the care provider in forming a differential diagnosis. Onset of marked obesity during early infancy raises the suspicion for function-altering genetic mutations affecting the leptin signalling pathway, but these are exceedingly rare conditions, with the most common, melanocortin-4 receptor defects, comprising

Figure 3. Complications associated with childhood obesity

Image obtained by dual energy X-ray absorptiometry from a teenage girl with BMI 38 kg/m2. Conditions that are of high prevalence and are well-established in their association with childhood obesity are shown in larger font size.

Figure 4. Operations performed for weight loss

(A) Roux-en-Y gastric bypass, (B) Adjustable gastric band. (Reprinted from Inge TH, Zeller MH, Lawson ML, Daniels SR. A critical appraisal of evidence supporting a bariatric surgical approach to weight management for adolescents. J Pediatr 2005;147(1):10-9 with permission from Elsevier Limited.)