A hypothesis linking the energy demand of the brain to obesity risk

We propose that variation in brain energy expenditure during childhood is an unexplored but important influence on obesity risk. This hypothesis is supported by evidence that the energy required by the developing brain decreases in later childhood as the rate of body weight gain is increasing. The hypothesis is further supported by findings of genetic and brain imaging research indicating a trade-off between the body mass index (BMI) and the volume of cortical and subcortical structures, and inverse associations between BMI and energetically costly executive cognitive functions. Efforts to quantify variability in brain energy use across children could inspire new educational strategies that increase brain energy demands and thereby reduce obesity risk. The causes of obesity are complex and multifactorial. We propose that one unconsidered but likely important factor is the energetic demand of brain development, which could constrain energy available for body growth and other functions, including fat deposition. Humans are leanest during early childhood and regain body fat in later childhood. Children reaching this adiposity rebound (AR) early are at risk for adult obesity. In aggregate data, the developing brain consumes a lifetime peak of 66% of resting energy expenditure in the years preceding the AR, and brain energy use is inversely related to body weight gain from infancy until puberty. Building on this finding, we hypothesize that individual variation in childhood brain energy expenditure will help explain variation in the timing of the AR and subsequent obesity risk. The idea that brain energetics constrain fat deposition is consistent with evidence that genes that elevate BMI are expressed in the brain and mediate a trade-off between the size of brain structures and BMI. Variability in energy expended on brain development and function could also help explain widely documented inverse relationships between the BMI and cognitive abilities. We estimate that variability in brain energetics could explain the weight differential separating children at the 50th and 70th BMI-for-age centiles immediately before the AR. Our model proposes a role for brain energetics as a driver of variation within a population?s BMI distribution and suggests that educational interventions that boost global brain energy use during childhood could help reduce the burden of obesity.