Why do humans undergo an adiposity rebound? Exploring links with the energetic costs of brain development in childhood using MRI-based 4D measures of total cerebral blood flow

Jacob E Aronoff,Can Wu,Christopher W Kuzawa,Michael Markl,Ali Shaibani,Susanne Schnell,Ann Ragin,Clancy Blair

doi:10.1038/s41366-022-01065-8

Abstract

BackgroundIndividuals typically show a childhood nadir in adiposity termed the adiposity rebound (AR). The AR serves as an early predictor of obesity risk, with early rebounders often at increased risk; however, it is unclear why this phenomenon occurs, which could impede understandings of weight gain trajectories. The brain’s energy requirements account for a lifetime peak of 66% of the body’s resting metabolic expenditure during childhood, around the age of the AR, and relates inversely to weight gain, pointing to a potential energy trade-off between brain development and adiposity. However, no study has compared developmental trajectories of brain metabolism and adiposity in the same individuals, which would allow a preliminary test of a brain-AR link.MethodsWe used cubic splines and generalized additive models to compare age trajectories of previously collected MRI-based 4D flow measures of total cerebral blood flow (TCBF), a proxy for cerebral energy use, to the body mass index (BMI) in a cross-sectional sample of 82 healthy individuals (0–60 years). We restricted our AR analysis to pre-pubertal individuals (0–12 years, n = 42), predicting that peak TCBF would occur slightly after the BMI nadir, consistent with evidence that lowest BMI typically precedes the nadir in adiposity.ResultsTCBF and the BMI showed inverse trajectories throughout childhood, while the estimated age at peak TCBF (5.6 years) was close but slightly later than the estimated age of the BMI nadir (4.9 years).ConclusionsThe timing of peak TCBF in this sample points to a likely concordance between peak brain energetics and the nadir in adiposity. Inverse age trajectories between TCBF and BMI support the hypothesis that brain metabolism is a potentially important influence on early life adiposity. These findings also suggest that experiences influencing the pattern of childhood brain energy use could be important predictors of body composition trajectories.

Highlights

In humans, fat stores typically decrease from infancy to childhood, reach a nadir in middle childhood, and rebound as adiposity begins to increase from adolescence into adulthood
Human brain development involves overproduction reflects the fact that the body mass index (BMI) captures both lean and fat tissue and of energetically demanding synaptic connections, which peak in that, unlike fat stores, lean mass is not lost at the nadir but density in childhood and is followed by experience-dependent continues to increase in parallel with linear growth
We report the relationship between BMI and total cerebral blood flow (TCBF) across the full sharply until the peak around age 5 years

Summary

Introduction

Fat stores typically decrease from infancy to childhood, reach a nadir in middle childhood, and rebound as adiposity begins to increase from adolescence into adulthood. At the brain’s lifetime peak energy expenditure at 4–5 years of age, its rate of glucose consumption accounts for an estimated 66% of the body’s resting energy expenditure, or SUBJECTS AND METHODS The data used here include measures of TCBF and BMI (kg/m2) obtained from roughly three times the fraction of the body’s metabolism devoted to the brain in adulthood (20–25%) [10].

Results

Conclusion