Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective.
Although variation in individual lifestyle and genotype are important factors in explaining individual variation in the risk of developing obesity in an obesogenic environment, there is growing evidence that developmentally plastic processes also contribute. These effects are mediated at least in part through epigenetic processes. These developmental pathways do not directly cause obesity but rather alter the risk of an individual developing obesity later in life. At least two classes of developmental pathway are involved. The mismatch pathway involves the evolved adaptive responses of the developing organism to anticipated future adverse environments, which have maladaptive consequences if the environment is mismatched to that predicted. This pathway can be cued by prenatal undernutrition or stresses that lead the organism to forecast an adverse future environment and change its developmental trajectory accordingly. As a result, individuals develop with central and peripheral changes that increase their sensitivity to an obesogenic environment. It provides a model for how obesity emerges in populations in rapid transition, but also operates in developed countries. There is growing experimental evidence that this pathway can be manipulated by, for example, postnatal leptin exposure. Secondly, maternal diabetes, maternal obesity and infant overfeeding are associated with a greater risk of later obesity. Early life offers a potential point for preventative intervention.
Gluckman
P D
PD
Liggins Institute, The University of Auckland, Auckland, New Zealand. pd.gluckman@auckland.ac.nz
Hanson
M A
MA
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D044127:Epigenesis, Genetic; D047109:Fetal Development / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000196:embryology; D006801:Humans; D020738:Leptin / Q000494:pharmacology; D009765:Obesity / Q000235:genetics*; D051381:Rats; D012307:Risk Factors
D020738:Leptin