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

Abstract

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.

The development of executive function in early childhood is inversely related to change in body mass index: Evidence for an energetic tradeoff?

“…The intercepts for BMI and EF were unrelated, indicating that the association was not present at baseline, but emerged developmentally. Given the young age of the sample, we interpret this finding as support for the hypothesized energetic trade‐off between brain development and fat deposition in early childhood (Kuzawa and Blair, ). Specifically, we propose that inversely correlated change between BMI and EF reflects an aspect of development in which between‐child variation in the energy demand of the developing brain affects between‐child variation in fat deposition at a time when children are typically losing fat mass in advance of the adiposity rebound (Rolland‐Cachera et al, ).…”

“…This analysis found that the percent of resting metabolic rate (RMR) accounted for by the brain increases rapidly in early childhood and peaks, at 66% of RMR, as normative weight gain velocity is decreasing in advance of the adiposity rebound. This finding inspired the hypothesis of an individual level brain–body energetic trade‐off between brain development and fat deposition during childhood (Kuzawa and Blair, ). Although little is currently known about between‐person variability in the energy demands of the developing brain, an inverse association in early childhood between change in BMI and change in EF, as a proxy for brain development in energetically costly prefrontal cortex (PFC), would be consistent with the hypothesis of a brain–body energetic trade‐off in childhood.…”

Childhood obesity: rapid weight gain in early childhood and subsequent cardiometabolic risk

“…Kuzawa and Blair ( 55 ) recently proposed a remarkable hypothesis linking the energy demand of the brain to obesity risk. The brain consumes about 40% of daily energy expenditure in early childhood (compared to 20% for adults), and glucose alone cannot supply this energy.…”

“…This means that brain energy expenditure is inversely related to body fat gain. Thus, this hypothesis states that brain energy expenditure helps to explain variation in the timing of AR ( 55 , 56 ).…”

Implications of late adiposity rebound

“…7 It is possible that the increased energy demand for the developing brain in early childhood is related to late adiposity rebound (reduced insulin resistance). 8,9 Therefore, it is important to clarify the importance of late adiposity rebound not only from the viewpoint of the path to obesity, but also from the perspective of development of brain health in children.…”