Lipase inhibitor orlistat decreases incorporation of eicosapentaenoic and docosahexaenoic acids in rat tissues

Orlistat is a gastric and pancreatic lipases inhibitor that is often prescribed to obese subjects. Orlistat has been shown to decrease the absorption of biologically important lipophilic micronutrients such as liposoluble vitamins. We hypothesized that long-term administration of orlistat may lower the incorporation of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in blood lipids and tissues. This hypothesis was tested in rats fed a diet supplemented with fish oil as a source of n-3 LC-PUFA. Male Wistar rats (n = 18) were divided into 3 groups and fed experimental high-fat diets containing fish oil (control diet) or fish oil plus orlistat (200 and 400 mg/kg of diet) over the course of 3 weeks. Fat absorption and the level of eicosapentaenoic acid (EPA) and docosahexaenoic acid, among other fatty acids, in red blood cells, plasma, liver, and spleen, were measured at the end of the experimental period. The results show that at 200 mg and 400 mg/kg of diet orlistat lowers fat absorption by 9% (P = .008) and 54% (P = .008). Orlistat given at the higher level induced a reduction of the incorporation of EPA in red blood cell (−45%; P = .006) and in plasma (−34%; P = .026) compared to the control group. Our results confirmed that administration of orlistat reduces incorporation of n-3 LC-PUFA in blood lipids and tissues in a rat model.