text: 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.
  Cetilistat has a bicyclic structure but lacks the β-lactone ring. It acts in a similar way as a typical lipase inhibitor that has the β-lactone structure.