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Orlistat and the Influence on Appetite Signals

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Handbook of Behavior, Food and Nutrition

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Abstract

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.

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Abbreviations

AgRP:

Agouti-related peptide

Alpha-MSH:

Alpha-melanocyte-stimulating hormone

Apo A-IV:

Apolipoprotein A-IV

BMI:

Body mass index

BNRP:

Bombesin/bombesin-related peptide

CART:

Cocaine- and amphetamine-regulated transcript

CCK:

Cholecystokinin

CCK1R:

CCK-1 receptor

CNS:

Central nervous system

CRF:

Corticotropin-releasing factor

DPP-4:

Dipeptidyl-peptidase-4

FFA:

Free fatty acid

GHRH:

Growth hormone-releasing hormone

GHS:

Growth hormone secretagogue

GI:

Gastrointestinal

GIP:

Gastric inhibitory polypeptide

GIPR:

Gastric inhibitory polypeptide receptor

GLP-1:

Glucagons-like peptide 1

GLP-2:

Glucagon-like peptide 2

kJ:

Kilo joule

MCH:

Melanin-concentrating hormone

MG:

Monoglyceride

NPY:

Neuropeptide Y

OLETF:

Otsuka-Long-Evans-Tokushima-Fatty rat

OXM:

Oxyntomodulin

PP:

Pancreatic polypeptide

POMC:

Pro-opiomelanocortin

PYY:

Peptide YY

THL:

Tetrahydrolipstatin

TG:

Triglyceride

VAS:

Visual analogue scales

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Medicine I, University Hospital Schleswig Holstein, Campus Kiel, Schittenhelmstr 12, 24105, Kiel, Germany

    Mark Ellrichmann

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  1. Mark Ellrichmann
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Correspondence to Mark Ellrichmann .

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Editors and Affiliations

  1. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

  2. Arizona Health Science Center, Mel and Enid Zuckerman College of Public, University of Arizona, 1501 N. Campbell Ave. Room 4335, Tucson, 85724-5155, Arizona, USA

    Ronald Ross Watson

  3. University of the West of Scotland, Ayr Campus, Ayr, KA8 0SR, United Kingdom

    Colin R. Martin

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Ellrichmann, M. (2011). Orlistat and the Influence on Appetite Signals. In: Preedy, V., Watson, R., Martin, C. (eds) Handbook of Behavior, Food and Nutrition. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92271-3_86

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