Treatment with the ghrelin-O-acyltransferase (GOAT) inhibitor GO-CoA-Tat reduces food intake by reducing meal frequency in rats.
The ghrelin acylating enzyme ghrelin-O-acyltransferase (GOAT) was recently identified and implicated in several biological functions. However, the effects on food intake warrant further investigation. While several genetic GOAT mouse models showed normal food intake, acute blockade using a GOAT inhibitor resulted in reduced food intake. The underlying food intake microstructure remains to be established. In the present study we used an automated feeding monitoring system to assess food intake and the food intake microstructure. First, we validated the basal food intake and feeding behavior in rats using the automated monitoring system. Afterwards, we assessed the food intake microstructure following intraperitoneal injection of the GOAT inhibitor, GO-CoA-Tat (32, 96 and 288 μg/kg) in freely fed male Sprague-Dawley rats. Rats showed a rapid habituation to the automated food intake monitoring system and food intake levels were similar compared to manual monitoring (P = 0.43). Rats housed under these conditions showed a physiological behavioral satiety sequence. Injection of the GOAT inhibitor resulted in a dose-dependent reduction of food intake with a maximum effect observed after 96 mg/kg (-27%, P = 0.03) compared to vehicle. This effect was delayed in onset as the first meal was not altered and lasted for a period of 2 h. Analysis of the food intake microstructure showed that the anorexigenic effect was due to a reduction of meal frequency (-15%, P = 0.04), whereas meal size (P = 0.29) was not altered compared to vehicle. In summary, pharmacological blockade of GOAT reduces dark phase food intake by an increase of satiety while satiation is not affected.
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany.
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P
Teuffel
CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division at the University of California Los Angeles, and Veterans Affairs Greater Los Angeles Health Care System, CA, USA.
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L
Wang
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany.
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P
Prinz
Department of Internal Medicine and Institute of Neurogastroenterology, Martin-Luther-Krankenhaus, Berlin, Germany.
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M
Goebel-Stengel
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany.
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S
Scharner
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany.
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P
Kobelt
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany.
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T
Hofmann
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany.
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M
Rose
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany.
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BF
Klapp
CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division at the University of California Los Angeles, and Veterans Affairs Greater Los Angeles Health Care System, CA, USA.
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JR
Reeve
Charite Center for Internal Medicine and Dermatology, Division of General Internal and Psychosomatic Medicine, Charite-Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany. andreas.stengel@charite.de.
A
A
Stengel
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D054439:Ghrelin / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000187:drug effects
D001067:Appetite Depressants; D004791:Enzyme Inhibitors; C554860:GO-CoA-Tat; D054439:Ghrelin; D010455:Peptides; D000217:Acyltransferases; C534462:ghrelin O-acyltransferase, rat