Animals with a genetic predisposition for obesity or with obesity-producing hypothalamic lesions exhibit a high efficiency of dietary energy retention. The metabolic basis for this high efficiency of energy retention has been actively pursued for several decades.
Brown adipose tissue(BAT) was found to be a major site for nonshivering and for diet-induced thermogenesis in rodents and the sympathetic nervous system(SNS) is the regulator of BAT thermogenesis. Results from the research during the 1980's directed interest toward the SNS as a possible mediator of reduced thermogenesis in obese animals. Since some obese animals were known to be cold sensitive, it was speculated that low sympathetic nervous system stimulation of BAT contributed to their obesity.
Dietary manipulations such as fasting or overfeeding by offering animals a sucrose solution were shown to affect SNS activity in heart, pancreas and liver of normal rats. These findings raised the possibility that dietary factors may differently affect the SNS in obese and lean animals.
Hypothalamus was suggested to be a control center for the SNS. Lesions in ventromedial hypothalamus(VMH) generally produce hyperphagia, hyperinsulinemia and reduce SNS activity. VMH lesioned animals become obese even when their intake is restricted to that of controls indicating increased metabolic efficiency in the lesioned animals. In contrast, lateral hypothalamus(LH) lesion produces large decreases in food intake and increases in metabolic rate mediated, in part, by increased SNS activity.
The observed abnormalities in norepinephrine kinetics in BAT of ob/ob moce, fa/fa rats and animals with obesity-producing lesions in the hypothalamus point to a role for the SNS in the development of obesity in these animals. However, caution is needed because there are situations where obesity develops in th absence of any apparent abnormalities in sympathetic stimulation of BAT. These situations will be discussed in more detabil. Increased attention should be directed to other organs.