Genetically obese rodents, widely used as animal models of early-onset obesity and diabetes, have a large number of metabolic and endocrine deficiencies. This proposal deals with deficiencies in the regulation of energy balance. Obese animals tend to have a low body temperature and low metabolic rate, and they produce less heat than lean animals during a meal and during cold exposure. The energy saved in thermogenesis is stored as fat. These deficits have been attributed to faulty brown fat metabolism. The hypothesis of the present work is that central control mechanisms of temperature regulation may contribute to energy balance disequilibrium. Many observations regarding obese animals are consistent with the idea that the regulatory has been re-set to a lower level. Hypothalamic thermosensitivity will be examined by measuring oxygen consumption and dry and evaporative heat loss during hypothalamic heating and cooling at different ambient temperatures in lean and obese Zucker rats. Inferences can be drawn from these measurements regarding the thermoregulatory set point and the gain of the regulator.
