Orlistat and the Influence on Appetite Signals

  • Mark Ellrichmann


Intestinal lipase inhibition using orlistat( tetrahydrolipstatin) has been widely used in the pharmacotherapy of morbid obesity. By blocking the active site of lipases, orlistat inhibits the hydrolysis of dietary triglycerides (TG) into monoglycerides (MG) and free fatty acids (FFA), and thus reduces the intestinal absorption of these lipolysis products. The formulation of the drug was licensed for the treatment of morbid obesity at the standard prescription dose of 120 mg three times daily prior to a meal. At this dose, orlistat prevents approximately 30% of the total ingested dietary fat from being absorbed. The secretion of gastrointestinal hormones from enteroendocrine cells is primarily controlled by the absorption of nutrients from the gut. Several studies have been conducted investigating the effect of lipase inhibition on the meal-mediated release of enteroendocrine hormones and regulation of appetite. Intestinal lipase inhibition by orlistat significantly lowers the postprandial secretion of CCK, GLP-1, PYY, PP, and GIP. Conversely, several groups have suggested that orlistat administration prevents the postprandial decrease in ghrelin levels. Leptin levels are only indirectly affected by orlistat treatment through its weight-lowering potential. Taken together, these alterations in gastrointestinal hormone concentrations can cause increased appetite sensations and greater food consumption and may therefore counteract the weight-lowering effect of orlistat.


Ghrelin Level Pancreatic Polypeptide Gastric Inhibitory Polypeptide Lipase Inhibition Gallbladder Emptying 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Agouti-related peptide


Alpha-melanocyte-stimulating hormone

Apo A-IV

Apolipoprotein A-IV


Body mass index


Bombesin/bombesin-related peptide


Cocaine- and amphetamine-regulated transcript




CCK-1 receptor


Central nervous system


Corticotropin-releasing factor




Free fatty acid


Growth hormone-releasing hormone


Growth hormone secretagogue




Gastric inhibitory polypeptide


Gastric inhibitory polypeptide receptor


Glucagons-like peptide 1


Glucagon-like peptide 2


Kilo joule


Melanin-concentrating hormone




Neuropeptide Y


Otsuka-Long-Evans-Tokushima-Fatty rat




Pancreatic polypeptide




Peptide YY






Visual analogue scales



Juris J. Meier and Wolfgang E. Schmidt are acknowledged for helpful comments and critical discussion of the manuscript.


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Medicine IUniversity Hospital Schleswig HolsteinKielGermany

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