Potato protease inhibitors inhibit food intake and increase circulating cholecystokinin levels by a trypsin-dependent mechanism

OBJECTIVE: To investigate the mechanisms underlying the satiety-promoting effects of a novel protease inhibitors concentrate derived from potato (PPIC). METHODS: Acute and prolonged effects of oral PPIC administration (100 mg/kg per day) on food intake, body weight, and gastric emptying were evaluated in healthy rats. Parameters of body weight, food intake, plasma glucose, insulin, and cholecystokinin (CCK) were measured. Duodenal proteolytic activity and CCK expression were determined in tissue extracts. Intestinal STC-1 cell culture model was used to investigate the direct effect of PPIC on CCK transcript level and secretion. RESULTS: Acute oral administration of PPIC reduced immediate food intake during the first two hours following the treatment, delayed gastric emptying, and decreased proteolytic activity in the duodenum. Repeated oral ingestion of PPIC reduced weight gain in male rats and significantly elevated the plasma CCK levels. Although duodenal mucosal CCK mRNA levels increased in response to PPIC administration, the concentrate failed to elevate CCK expression or release in STC-1 cells. The 14-day ascending dose range study (33 to 266 mg/kg PPIC per day) showed no adverse side effects associated with PPIC administration. CONCLUSION: These findings provided evidence that PPIC is effective in reducing food intake and body weight gain in healthy rats when administered orally by increasing circulating CCK levels through a trypsin-dependent mechanism.