Functional Statement for the SGO

The primary goal of the Section on Growth and Obesity is to elucidate the genetic underpinnings of the metabolic and behavioral endophenotypes that contribute to the development of obesity in children. Using an integrated program of basic and clinical translational research, our ongoing studies of patients with monogenic and polygenic obesity and volunteer children of all weight strata aim to advance our understanding of energy balance regulation during childhood. Using our unique longitudinal cohorts of children who have undergone intensive metabolic and behavioral phenotyping, we examine genetic and phenotypic factors predictive of progression to adult obesity in children who are in the “pre-obese” state, allowing characterization of phenotypes unconfounded by the impact of obesity itself. Once identified as linked to obesity, genetic variants that impair gene function are studied intensively. These approaches are expected to improve our ability to predict which children are at greatest risk for obesity and its comorbid conditions and to lead to more targeted, etiology-based prevention and treatment strategies for pediatric obesity.

Objectives

1. To investigate the genetic, physiologic, metabolic, behavioral, and environmental characteristics leading to obesity in diverse US populations.
2. To devise population-specific risk predictors to enable identification of children and adults at risk for the development of obesity and its complications.
3. To use this information to develop rational interventions specifically targeted to prevent and treat obesity.

Introduction

For children in the US, the prevalence of overweight has more than tripled during the past four decades. In 2015-2016, 18.5 percent of children and adolescents were considered to have obesity (Body Mass Index, BMI ≥95th percentile), and an additional 16.6 percent were classified as having overweight (BMI 85-95th percentile). Racial and ethnic minority populations, especially African American, Hispanic/Latina, and American Indian women, are at particular risk for the development of obesity. While adult obesity has also increased dramatically, the increase in obesity prevalence among children is particularly alarming. Obesity-related diseases rarely seen in children previously, including obesity-associated sleep apnea, non-alcoholic fatty liver disease with resultant cirrhosis and type 2 diabetes, are increasingly diagnosed in pediatric patients. The earlier onset of chronic health conditions such as type 2 diabetes in childhood has been shown to lead to an earlier onset of related medical complications such as end-stage renal disease. Pediatric obesity also has a tremendous impact on later health, in some cases even independent of adult weight. In the absence of effective strategies to prevent and treat childhood obesity, millions of children will enter adulthood with the physical and psychological consequences of excess adiposity. The current U.S. childhood obesity epidemic also has the potential to reverse the improvements in life-expectancy that have been seen during the 20th century in the U.S. and to result in more functional disability and decreased quality of life in those who survive to old age.

The alarming rise in obesity in both children and adults has occurred at a time when the current environment affords easy access to large portions of calorie-dense foods and requires less voluntary energy expenditure. However, this environment leads to obesity only in those individuals whose body weight regulatory systems are not able to control body adiposity with sufficient precision in our high calorie/low activity environment. Indeed, the most marked increases in BMI are found in children at the greatest BMI percentiles, and it is clear there is variability within the U.S. population in susceptibility to weight gain that is not fully explained by sociocultural or environmental factors. Even today, 60-80% of the variance in pediatric body weight can be attributed to genetic factors.

Effective prevention and treatment of obesity-related disorders requires a better understanding of the key elements for body weight regulation. The Section on Growth and Obesity carries out an integrated program of basic and clinical translational research aimed at: 1) elucidating genetic underpinnings of the metabolic and behavioral endophenotypes involved in energy homeostasis during childhood, and 2) identifying effective strategies for the prevention and treatment of obesity and its comorbid conditions.