Regulation of thermogenesis in obesity.

Obesity results when the intake of energy exceeds that which is expended with the resultant storage of the excess energy as fat. Thermogenesis, the metabolic expenditure of energy as heat, is the primary way in which mammals loss dietarily-derived energy and some evidence suggests that certain obese humans may have defective diet-induced thermogenesis. The sympathetic nervous system is the primary effector of thermogenesis through the release of norepinephrine at its nerve terminals. During the early stages of over-eating, there is an increase in sympathetic activity in several organs, including brown adipose tissue (BAT), a major thermogenic organ in many mammals. This increased neural activity is associated with increased thermogenic capacity of the entire animal as well as in BAT and, together, these events are sufficient to prevent the development of obesity in certain young animals such as rats. However, in older rats, obesity eventually develops over several months' of exposure to high energy diets and the early increases in thermogenic capacity and sympathetic activity return to or below baseline levels. Also, genetically obese rodents generally have defective total body and BAT thermogenic capacity, especially to a dietary challenge, as well as abnormal sympathetic function in their BAT. These observations suggest that there are certain types of obesity that are associated with a diminished ability to expend dietarily-derived energy as heat and that chronic obesity in general represents an altered homeostatic state associated with increased metabolic efficiency in some humans and other mammals.