Obesity and Metabolism

Editor(s): Korbonits M. (London) 
Table of Contents
Vol. 36, No. , 2008
Section title: Paper
Korbonits M (ed): Obesity and Metabolism. Front Horm Res. Basel, Karger, 2008, vol 36, pp 61-72

Fetal and Neonatal Pathways to Obesity

Gluckman P.a,c · Hanson M.d · Beedle A.a · Raubenheimer D.a,b
aCentre for Human Evolution, Adaptation and Disease, Liggins Institute, b School of Biological Sciences, University of Auckland, and c National Research Centre for Growth and Development, Auckland, New Zealand; d Institute of Developmental Sciences, University of Southampton, Southampton, UK


Evolutionary and developmental perspectives add considerably to our understanding of the aetiology of obesity and its related disorders. One pathway to obesity represents the maladaptive consequences of an evolutionarily preserved mechanism by which the developing mammal monitors nutritional cues from its mother and adjusts its developmental trajectory accordingly. Prediction of a nutritionally sparse environment leads to a phenotype that promotes metabolic parsimony by favouring fat deposition, insulin resistance, sarcopenia and low energy expenditure. But this adaptive mechanism evolved to accommodate gradual changes in nutritional environment; rapid transition to a situation of high energy density results in a mismatch between predicted and actual environments and increased susceptibility to metabolic disease. This pathway may also explain why breast and bottle feeding confer different risks of obesity. We discuss how early environmental signals act through epigenetic mechanisms to alter metabolic partitioning, glucocorticoid action and neuroendocrine control of appetite. A second pathway involves alterations in fetal insulin levels, as seen in gestational diabetes, leading to increased prenatal fat mass which is subsequently amplified by postnatal factors. Both classes of pathway may coexist in an individual. This developmental approach to obesity suggests that potential interventions will vary according to the target population.

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