Fig. 2.

The match-mismatch paradigm of metabolic disease. The developing organism senses maternally transmitted environmental cues, such as undernutrition, during prenatal and early postnatal life. Developmental plasticity in response to these cues modifies the default trajectory defined by the inherited fetal genome and epigenome according to whether the environment is perceived as adequate (dark background) or deprived (light background), resulting in adjustment of metabolic set points. If the eventual mature environment, whether adequate or deprived, matches the prediction, then the risk of metabolic disease in later life is low. If there is a mismatch between the predicted and actual mature environments, particularly if the mature environment is richer than anticipated, then the risk of metabolic disease is enhanced. [Reproduced from P. D. Gluckman et al.: Am J Hum Biol 19:1–19, 2007 (23). © 2006 Wiley-Liss, Inc.; reprinted with permission from John Wiley & Sons, Inc.]