Physiological and behavioral studies of the effects of various interventions on the ponderostatic set-point.

摘要

This thesis aims at verifying whether the set-point for body weight can be modified by pharmacological, behavioral, or surgical manipulation. We first injected rats with nicotine and measured their threshold for hoarding food to verify the potential of using direct-acting cholinergic activity to lower the set-point for body weight. Results showed that low dose nicotine (0.02 & 0.05 mg/kg, i.p.) significantly lowered the body weight set-point (p = 0.027 & p = 0.001) when compared to control saline treatment. In another experiment on set-point, we increased the palatability of rats' food in order to measure the effect on the food hoarding threshold. Increasing the palatability of food significantly raised the body weight (p = 0.002). In this same experiment, the rats were maintained on a cafeteria diet and made obese. Their threshold for hoarding was significantly increased (p = 0.001) indicating a raised set-point. In humans, we measured the effect of moderate weight loss in clinically obese subjects following a commercial dietary regimen. In our obese subjects, satiety was significantly accelerated (p = 0.0028) after weight loss (p 0.0001), thus showing a lowered body weight set-point. Again in rats, we created a biliopancreatic bypass in gastrointestinal tract, an operation similar to that for human morbid obesity. The bypass surgery significantly lowered the body weight set-point (p = 0.02), but only in rats rendered obese on a cafeteria diet. In the final experiment, we assessed the effects of biliopancreatic bypass with duodenal switch in a group of morbidly obese subjects as practiced for over twenty years at Hopital Laval, on body weight and satiety. After obesity surgery, operated patients showed a significantly lowered body weight (p 0.0001) and an earlier satiety (p = 0.0004) than weight matched controls thus suggesting a lowered body weight set-point. The surgical technique for morbid obesity assures patients a return to normal satiation while lowering the body weight set-point. Taken together, these results confirm that there exists a set-point for body weight, and that it is possible to lower it for therapeutic purposes.