Childhood obesity prevention from cell to society Barbara H. Fiese 1 , Kelly K. Bost 1 , Brent A. McBride 1 , and Sharon M. Donovan 2 1 Department of Human and Community Development, University of Illinois, Urbana, IL 61801, USA 2 Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801, USA Nearly 40% of US children are overweight or obese. We propose that a cell-to-society integrative approach is needed that takes into account biology, early child de- velopment, home and childcare environments, and pub- lic policy. This approach requires researchers, families, and policy makers to work together to develop preven- tative strategies and interventions that benefit the nu- trition and wellbeing of young children and their families, and ultimately the health of the nation. Childhood obesity prevention from cell to society Recent estimates of obesity prevalence in US children categorized 27% of children aged 2–5 years as overweight [body mass index (BMI) >85th percentile] and 12% as obese (>95th percentile) [1]. Overweight and obesity dur- ing early childhood are strong predictors of persistence into later childhood, adolescence, and adulthood. Because life- style habits are established early in life, the maintenance of unhealthy body weight from childhood into later years may explain, in part, the relatively poor success of stem- ming the tide of childhood obesity. The simple explanation for overweight, that more calo- ries are consumed than expended, belies the complex interaction of biological risk factors, early feeding prac- tices, where children live and play, and the intersection of food policies with family life. The rapid increase in obesity over the past two decades suggests that change in the food and physical environment and its interaction with biologi- cal factors has contributed to unhealthy weight gain in early childhood. Without an integrated approach, it is unlikely that meaningful strides will be made in reducing the prevalence of obesity. We provide a brief overview of how a cell-to-society approach used in our STRONG Kids Program [2] may guide transdisciplinary research and prevention planning (see Glossary; Figure 1). The Six Cs ecological model extends previous theoretical models on childhood weight imbalance by acknowledging dimensions of factors specific to heredity as well as the environment, to activity as well as nutrition, to resources and opportunities as well as practices, and to development from birth through adolescence. Outside the cell and child spheres, the model focuses on factors that can be modified by education, interventions, or public policy [2]. Individual biology and childhood obesity At the center of this conceptual framework is the cell, representing the genetic risk for obesity and the contribu- tion of the microbiome. Variation in how individuals respond to the same environmental conditions indicates that innate biology is key to obesity development. Genome- wide association studies have identified over 20 genes associated with BMI [3]: single-nucleotide polymorphisms (SNP) in these vulnerability genes can place a child at risk for obesity. For example, a SNP in the FTO (fat mass and obesity-associated) gene is correlated to higher BMI and adiposity [4]. Epigenetics has suggested new mechanisms to explain variation in susceptibility to developing obesity. Epigenetic modulation of gene expression represents a means whereby a fetus can be programmed in utero to adapt to the external environment. These non-sequence modifications may become heritable and, in countries un- dergoing the nutrition transition, the epigenome of a child may bear the signature of undernutrition and hence be mismatched with the greater availability of food. Lastly, the gut microbiota is a ‘super-organ’ with unique capability to adapt to environmental challenges and influence energy homeostasis of the host. Differences in the proportions of the two major bacterial phyla (Firmicutes-to-Bacteroi- detes) have been associated with obesity in adults and animal models, however, less is known about these asso- ciations in children [5]. A Firmicutes-to-Bacteroidetes ratio difference is present as early as 3 months of age in breast- versus formula-fed infants, with the latter displaying the obese microbial phenotype [5]. Understanding the ante- cedents of childhood obesity will necessitate exploration of the interactions between genetic and epigenetic factors with external influences that form the Six Cs model [2]. Family relationships Specific feeding practices and routines can protect children from obesity. Beginning with breastfeeding, mothers respond to their infant’s signs of hunger. Every month that an infant is breastfed in the first 9 months decreases Forum: Science & Society Glossary Epigenetics: the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. Responsive feeding: feeding takes place in a pleasant environment free of distractions and occurs when the child is likely to be hungry. The caregiver attends to the hunger signals of the child and responds to the child in a prompt and emotionally supportive manner. Single-nucleotide polymorphism (SNP): genetic variation in a DNA sequence that occurs when a single nucleotide is altered; SNPs are considered to be point mutations that have been evolutionarily successful enough to be present in a significant proportion of the population of a species. Transdisciplinarity: a research strategy that crosses many disciplinary boundaries to create a holistic approach focused on problems that encompass two or more disciplines. Corresponding author: Donovan, S.M. (sdonovan@illinois.edu). Keywords: childhood obesity; transdisciplinary; public policy. 375