Cetilistat is a novel inhibitor of pancreatic
lipase. The aim of this report is to evaluate the anti-
obesity action of
cetilistat in diet-induced
obesity (DIO) rats.
Cetilistat inhibited rat and human pancreatic
lipase activity with an IC (50) of 54.8 nmol/l, and 5.95 nmol/l, respectively, meaning that it is 9.2 times more potent for human pancreatic
lipase than for that of rat.
Cetilistat was orally administered simultaneously with fat
emulsion to Sprague-Dawley rats. Plasma
triglyceride (TG) concentrations were measured before and after oral fat loading. The elevation in plasma
triglyceride concentration by oral fat loading was reduced by
cetilistat in a dose-dependent manner at 3, 10, 30, and 100 mg/kg, indicating that
cetilistat reduces intestinal fat absorption in rats.
Cetilistat was administered to DIO F344 rats as food admixture in a high-fat diet at 4.9, 14.9, or 50.7 mg/kg/day for three weeks. Both
triglyceride and nonesterified
fatty acid content in the feces were dose-dependently and drastically increased, suggesting the intestinal breakdown of fat and excretion.
Body weight (BW) gain and white adipose tissue (WAT) weight were reduced in a dose-dependent manner. In addition,
leptin, TG, and total
cholesterol (TC) in plasma were reduced and there were no reports of oily stools. These results suggest that
cetilistat ameliorates
obesity and
hyperlipidemia in DIO rats, a plausible animal model of the most common type of human
obesity.