Developmental origins of obesity: a sympathoadrenal perspective

Environmental exposures at crucial points in development permanently alter sympathoadrenal function in mammals. Both the sympathetic innervation of peripheral tissues and the responsiveness of sympathetic nerves and adrenal medulla to standard stimuli are susceptible to modification by exposures in early life. Several conditions studied in the laboratory, including environmental temperature, litter size and maternal nutrition, in addition to affecting sympathoadrenal function also produce larger, fatter offspring, raising the possibility that developmental programming of the sympathetic nervous system (SNS) may contribute to acquisition of an obese phenotype. The specific changes noted in all three circumstances include evidence of an increase in sympathetic innervation in pancreas and retroperitoneal fat. By contrast, SNS development is impaired in experimental models of intrauterine growth retardation. Although the physiological implications of increased sympathetic innervation in pancreas and retroperitoneal fat are not fully understood, these changes seen in animals reared at cool temperatures, in small litters or by mothers fed refined carbohydrate diets likely reflect an early enhancement of the offspring's capacity to take up and store glucose. If so, the tendency of these animals to gain weight and accumulate fat may represent an adaptive response to 'over-nutrition' in early life.