Body weight regulation in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Rats treated with a sublethal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 15 micrograms/kg) exhibited reduced feed intake and loss of body weight for the first 3 weeks after treatment. During the next 10 weeks, TCDD-treated rats maintained their body weight at a lower nearly constant percentage of that of control rats fed ad libitum. At no time did rats treated with TCDD exhibit hyperphagia which would have returned their weight to a normal level. Control rats pair-fed to TCDD-treated rats for more than 7 weeks displayed compensatory hyperphagia when permitted to feed ad libitum and their weight recovered to a near-normal level. The lower level of body weight in TCDD-treated animals was apparently due to a reduction in the regulation level or "set-point" for body weight. The following findings in TCDD-treated and control rats fed ad libitum supported this idea. First, when the reduced weight of the TCDD group was challenged by changes in the caloric density or palatability of the diet, TCDD-treated rats exhibited adjustments in feed intake and body weight that were essentially identical to those of control rats. Second, when body weight was manipulated by feeding a high-calorie diet or by restricting feed intake, both TCDD-treated and control rats quickly returned to weight levels from which they had been displaced. Third, carcass analyses conducted 7 weeks after treatment revealed that TCDD-treated rats had lower absolute amounts of body fat, protein, and water. However, when these constituents were expressed as percentages of total body weight no remarkable differences from the control were observed. Fourth, when TCDD-treated rats were induced to overeat and restore body weight to the same level as control rats fed ad libitum. TCDD-treated animals did not reassume a normal body composition but became obese. Obesity was also observed when control rats were induced to overeat. Thus, TCDD-treated rats regulate their body weight in the same fashion as control rats but at a weight regulation level or set-point that is markedly reduced.