page_title: Orlistat
section_title: Mechanism of action
hierarchical_section_title: Orlistat / Mechanism of action
caption_attribution_description: English: [X-ray_crystallography#Biological_macromolecular_crystallography
context_page_description: Orlistat is a drug designed to treat obesity. It is marketed as a prescription drug under the trade name Xenical by Roche in most countries, and is sold over-the-counter as Alli by GlaxoSmithKline in the United Kingdom and the United States. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It is intended for use in conjunction with a healthcare provider-supervised reduced-calorie diet.
  Orlistat is the saturated derivative of lipstatin, a potent natural inhibitor of pancreatic lipases isolated from the bacterium Streptomyces toxytricini. However, due to its relative simplicity and stability, orlistat was chosen over lipstatin for development as an anti-obesity drug.
  The effectiveness of orlistat in promoting weight loss is definite but modest. Pooled data from clinical trials suggest that people given orlistat in addition to lifestyle modifications, such as diet and exercise, lose about 2–3 kilograms more than those not taking the drug over the course of a year.
context_section_description: Orlistat works by inhibiting gastric and pancreatic lipases, the enzymes that break down triglycerides in the intestine. When lipase activity is blocked, triglycerides from the diet are not hydrolyzed into absorbable free fatty acids, and instead are excreted unchanged. Only trace amounts of orlistat are absorbed systemically; the primary effect is local lipase inhibition within the GI tract after an oral dose. The primary route of elimination is through the feces.
  Orlistat was also recently found to inhibit the thioesterase domain of fatty acid synthase (FAS), an enzyme involved in the proliferation of cancer cells but not normal cells. However, potential side effects of Orlistat, such as inhibition of other cellular off-targets or poor bioavailability, might hamper its application as an effective antitumor agent. One profiling study undertook a chemical proteomics approach to look for new cellular targets of orlistat, including its off-targets. Orlistat also shows potential activity against the Trypanosoma brucei parasite.
  At the standard prescription dose of 120 mg three times daily, before meals, orlistat prevents approximately 30% of dietary fat from being absorbed.  Higher doses do not produce more potent effects.
caption: Crystallographic structure of human fatty acid synthase (rainbow color, N-terminus = blue, C-terminus = red) inhibited by orlistat (space-filling model; carbon = grey, oxygen = red, nitrogen = blue).[28]
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