Lipase inhibitors

Lipase inhibitors are drugs used to reduce the activity of lipases found in the intestine. Lipases are secreted by the pancreas when fat is present. The primary role of lipase inhibitors is to decrease the gastrointestinal absorption of fats. Fats then tend to be excreted in feces rather than being absorbed to be used as a source of caloric energy, and this can result in weight loss in individuals. These inhibitors could be used for the treatment of obesity, which can subsequently lead to Type II diabetes and cardiovascular diseases if not managed. An example of a lipase inhibitor is orlistat.

Lipase inhibitors can be found naturally in plants and can be clinically modified to drugs. Some include Panax japonicas and Platycodi radix. These plants include phytochemicals such as saponins, polyphenols, flavonoids, and caffeine.

Mechanism
Lipase inhibitors may affect the amount of fat absorbed, yet they do not block the absorption of a particular type of fat. Likewise, lipase inhibitors are not absorbed into the bloodstream. Lipase inhibitors bind to lipase enzymes in the intestine, thus preventing the hydrolysis of dietary triglycerides into monoglycerides and fatty acids. This then reduces the absorption of dietary fat. Lipase inhibitors covalently bond to the active serine site on lipases. This covalent bond is strong, meaning the lipase inhibitor tends to remain attached to the lipase. Studies have shown that lipase inhibitors work optimally when 40% of an individual’s daily caloric intake is obtained from fat. Orlistat tends to block absorption of 30% of total fat intake from a meal, as orlistat passes out of the digestive tract more rapidly than fat does.

Side effects
Lipase inhibitors can cause side effects, including oily spotting, fecal incontinence, flatus with discharge and abdominal cramping. Additionally, a raise in blood pressure, dry mouth, constipation, headache, and insomnia have been reported. Malabsorption of fat soluble vitamins may develop as a result of the impaired absorption of fat, which is required for the transportation of these vitamins across the intestine to reach the blood. Since lipase inhibitors are not absorbed in the intestine, and consequently not circulating in the blood, information about alternative side effects such as the modulation of the gastrointestinal tract is unobtainable. Generally, side effects can be controlled by reducing the consumption of dietary fats. Overall, orlistat has been considered to be safer than other anti-obesity drugs.