Trypsin inhibitor effects on food intake and weight gain in Zucker rats

Decreased body weight and increased pancreas weight which occur in rats fed raw soybeans are thought to be due to the presence of trypsin inhibitors in the soybeans (SBTI). Since trypsin is postulated to be a negative feedback signal for cholecystokinin (CCK) secretion, SBTI may have these effects by increasing secretion of CCK. CCK is a putative satiety signal; thus, increased secretion of CCK could decrease food intake, and, if maintained over a period of time, body weight. In these experiments the effects of a trypsin inhibitor [N,N-dimethyl-carbamoyl 4-(4-guanidino-benzylyloxy)-phenyl acetate methane-sulfate (DGPM)]on feeding pattern were investigated in Zucker obese and lean rats. Administration of 25-200 mg/kg DGPM to 6-hr fasted rats decreased daily food intake by dose-dependently decreasing average meal size in both obese and lean rats, but the response was greater in obese rats. Administration of 100 mg/kg DGPM twice daily for 7 days decreased food intake and body weight in obese but not lean rats. Thus, these results suggest that decreased body weight associated with SBTI is due to decreased food intake partly as a result of increased secretion of the putative satiety peptide CCK.