Human digestive system
Chewing, in which food is mixed with saliva, begins the mechanical process of digestion. This produces a bolus which can be swallowed down the esophagus to enter the stomach. Here it is mixed with gastric acid until it passes into the duodenum where it is mixed with a number of enzymes produced by the pancreas. Saliva also contains a catalytic enzyme called amylase which starts to act on food in the mouth. Another digestive enzyme called lingual lipase is secreted by some of the lingual papillae on the tongue and also from serous glands in the main salivary glands. Digestion is helped by the chewing of food carried out by the muscles of mastication, by the teeth, and also by the contractions of peristalsis, and segmentation. Gastric acid, and the production of mucus in the stomach, are essential for the continuation of digestion.
Discovery and development of gastrointestinal lipase inhibitors
The lipase inhibitors lipstatin and orlistat act locally in the intestinal tract. They are minimally absorbed in the circulation because of their lipophilicity. Hence, they do not affect systemic lipases. 
The mechanism of lipase inhibitors in fat digestion is shown in figure 1. These inhibitors bind covalently as an ester to the serine hydroxyl group at the active site on pancreatic- and gastric lipases and form a stable complex.
This results in a conformational change in the enzyme which causes exposing of the catalytic active site. When the active site is exposed, the hydroxyl group on the serine residue is acylated. This leads to irreversible inactivation of the enzyme. 
The inactive lipase is incapable of hydrolysing fats into absorbable fatty acids and monoglycerides, therefore triglycerides are excreted undigested with faeces. With this mode of action calorie uptake from fat in food is limited, hence body weight is reduced. The main role of lipase inhibitors is therefore to inhibit lipases in the gastrointestinal tract, but they do not have significant activity against proteases, amylases or other digestive enzymes.