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Stengel A.,University of California at Los Angeles | Goebel M.,University of California at Los Angeles | Wang L.,University of California at Los Angeles | Rivier J.,La Jolla Salk Institute | And 3 more authors.
Physiology and Behavior | Year: 2010

We recently reported that the oligosomatostatin receptor agonist, ODT8-SST increases food intake in rats via the somatostatin 2 receptor (sst2). We characterized ingestive behavior following intracerebroventricular (icv) injection of a selective sst2 agonist in freely fed mice during the light phase. The sst2 agonist (0.01, 0.03, 0.1, 0.3 or 1μg/mouse) injected icv under short inhalation anesthesia dose-dependently increased cumulative light phase food intake over 4h compared to vehicle with a 3.1-times increase at 1μg/mouse (p<0.05). Likewise, the sst2,3,5 agonist octreotide (0.3 or 1μg/mouse) dose-dependently increased 4-h food intake, whereas selective sst1 or sst4 agonists at 1μg/mouse did not. In vehicle-treated mice, high fat diet increased caloric intake/4h by 2.8-times compared to regular diet (p<0.05) and values were further increased 1.4-times/4h by the sst2 agonist. Automated continuous assessment of food intake established a 6.6-times higher food intake during the dark phase due to increased number of meals, meal size, meal duration and rate of ingestion compared to non-treated mice during the light phase. During the first 4h post icv sst2 agonist injection, mice had a 57% increase in number of meals with a 60% higher rate of ingestion, and a 61% reduction in inter-meal intervals, whereas meal sizes were not altered compared to vehicle. These data indicate that the activation of brain sst2 receptors potently stimulates the light phase ingestive behavior under basal or high fat diet-stimulated conditions in mice. The shortened inter-meal interval suggests an inhibitory effect of the sst2 agonist on "satiety", whereas "satiation" is not altered as indicated by normal meal size. © 2010.

Teuffel P.,Universitaetsmedizin Berlin | Wang L.,University of California at Los Angeles | Prinz P.,Universitaetsmedizin Berlin | Goebel-Stengel M.,Institute of Neurogastroenterology | And 7 more authors.
Journal of Physiology and Pharmacology | Year: 2015

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 μg/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. © 2015 Polish Physiological Society. All rights reserved.

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