Interaction of perinatal and pre-pubertal factors with genetic predisposition in the development of neural pathways involved in the regulation of energy homeostasis.
A majority of human obesity is inherited as a polygenic trait. Once obesity develops, over 90% of individuals repeatedly regain lost weight after dieting. Only surgical interventions offer long lasting weight loss. Thus, clinical data suggest that some individuals have a predisposition to develop and maintain an elevated body weight set-point once they are provided with sufficient calories to gain weight. This set-point is mediated by an integrated neural network that controls energy homeostasis. Unfortunately, currently available tools for identifying obesity-prone individuals and examining the functioning of these neural systems have insufficient resolution to identify specific neural factors that cause humans to develop and maintain the obese state. However, rodent models of polygenically inherited obesity allow us to investigate the factors that both predispose them to become obese and that prevent or enhance the development of such obesity. Maternal obesity during gestation and lactation in obesity-prone rodents enhances offspring obesity and alters their neural pathways involved in energy homeostasis regulation. Early postnatal exposure of obesity-resistant offspring to the milk of genetically obese dams alters their hypothalamic pathways involved in energy homeostasis causing them to become obese when fed a high fat diet as adults. Finally, short-term exercise begun in the early post-weaning period increases the sensitivity to the anorectic effects of leptin and protects obesity-prone offspring from becoming obese for months exercise cessation. Such studies suggest that early identification of obesity-prone humans and of the factors that can prevent them from becoming obese could provide an effective strategy for preventing the world wide epidemic of obesity.
Levin
Barry E
BE
Neurology Service (127C), Veterans Administration Medical Center, and Department of Neurology and Neurosciences, New Jersey Medical School, E. Orange, Newark, NJ 07018-1095, USA. levin@umdnj.edu
D000818:Animals; D001921:Brain / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism*
D020738:Leptin