ESPE Yearbook of Paediatric Endocrinology

kuzawa@northwestern.edu Int J Obes (Lond). 2022 May;46(5):1044–1050. doi: 10.1038/s41366-022-01065-8. Epub 2022 Feb 8. https://pubmed.ncbi.nlm.nih.gov/35136192/

Brief Summary: This cross-sectional study measured total cerebral blood flow (TCBF) by MRI in 82 healthy individuals (ages 0–60 years) to explore the association between TCBF and BMI over life. Of particular interest was the question whether the BMI nadir (adiposity rebound, AR) and TCBF are inversely related.

Adiposity rebound (AR) in early childhood is a risk factor for obesity in adolescence and adulthood [1]. Aronoff et al propose that there is a link between AR and the energetic demand of brain development. It is assumed that AR results from changes in body composition during infancy and childhood which are determined by a shift in energy balance. Shifts in energy balance during childhood are related to changes in level of physical activity, but also age-related changes in brain energy requirements have been shown [2,3]. A measure of brain energy requirement is the TCBF, which is closely coupled to local glucose metabolism [4,5]. Aronoff et al observed that TCBF and BMI were inversely correlated over the life course. In the subgroup of pre-pubertal children, the peak for the TCBF at 5.6 years was near the BMI nadir at 4.9 years of age. This observation is important, because it helps for a deeper understanding of life-course influences on body composition trajectories and related disease risk. This observation also highlights the brain as a potential pathway linking early life experiences with obesity risk. The authors hypothesize that early adversity and stressors could alter body composition trajectories by accelerating brain maturation, possible leading to an earlier peak in brain metabolism and resulting in an earlier AR and greater adiposity.

The strength of the present work is certainly the measurement of TCBF by MRI in a cohort including infants, children, adolescents and adults. The cross-sectional design is a limitation. To confirm the hypothesis that the AR is linked developmentally to the high energetic requirements of brain development at this age, longitudinal BMI and TCBF measures from birth onwards are necessary.

References: 1. Kansra AR, Lakkunarajah S, Jay MS. Childhood and Adolescent Obesity: A Review. Front Pediatr. 2021 Jan 12;8:581461. doi: 10.3389/fped.2020.581461. eCollection 2020. 2. Kuzawa CW, Blair C. A hypothesis linking the energy demand of the brain to obesity risk. Proc Natl Acad Sci USA. 2019 Jul 2;116(27):13266–13275. doi: 10.1073/pnas.1816908116. Epub 2019 Jun 17. 3. Kuzawa CW, Chugani HT, Grossman LI, Lipovich L, Muzik O, Hof PR, et al. Metabolic costs and evolutionary implications of human brain development. Proc Natl Acad Sci USA. 2014 Sep 9;111(36):13010–5. doi: 10.1073/pnas.1323099111. Epub 2014 Aug 25. 4. Lenz C, Frietsch T, Fütterer C, Rebel A, van Ackern K, Kuschinsky W, et al. Local coupling of cerebral blood flow to cerebral glucose metabolism during inhalational anesthesia in rats: desflurane versus isoflurane. J Am Soc Anesthesiologists. 1999;91:1720. 5. Lenz C, Rebel A, van Ackern K, Kuschinsky W, Waschke KF. Local cerebral blood flow, local cerebral glucose utilization, and flow-metabolism coupling during sevoflurane versus isoflurane anesthesia in rats. J Am Soc Anesthesiologists. 1998;89:1480–8.