The Obesity Epidemic: Metabolic Imprinting on Genetically Susceptible Neural Circuits

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Abstract
LEVIN, BARRY E. The obesity epidemic: metabolic im- printing on genetically susceptible neural circuits. Obes Res. 2000;8:342-347. The apparent obesity epidemic in the industrialized world is not explained completely by increased food intake or de- creased energy expenditure. Once obesity develops in ge- netically predisposed individuals, their obese body weight is avidly defended against chronic caloric restriction. In ani- mals genetically predisposed toward obesity, there are mul- tiple abnormalities of neural function that prime them to become obese when dietary caloric density and quantity are raised. Once obesity is fully developed, these abnormalities largely disappear. This suggests that obesity might be the normal state for such individuals. Formation of new neural circuits involved in energy homeostasis might underlie the near permanence of the obese body weight. Such neural plasticity can occur during both nervous system develop- ment and in adult life. Maternal diabetes, obesity, and undernutrition have all been associated with obesity in the offspring of such mothers, especially in genetically predis- posed individuals. Altered brain neural circuitry and func- tion often accompanies such obesity. This enhanced obesity may then be passed on to subsequent generations in a feed-forward, upward spiral of increasing body weight across generations. Such findings suggest a form of "met- abolic imprinting" upon genetically predisposed neural cir- cuits involved in energy homeostasis. Centrally acting drugs used for obesity treatment lower the defended body weight and alter the function of neural pathways involved in energy homeostasis. But they generally have no permanent effect on body weight or neural function. Thus, early identification of obesity-prone mothers, infants, and adults and treatment of early obesity may be the only way to prevent the forma- tion of permanent neural connections that promote and perpetuate obesity in genetically predisposed individuals.