Gastric electrical stimulation increases ghrelin production and inhibits catecholaminergic brainstem neurons in rats.
Gastric electrical stimulation (GES) is a new therapeutic option for functional dyspepsia and gastroparesis. In addition to ameliorating nausea and vomiting, GES results in improved appetite which is not always associated with accelerated gastric emptying. To explore the central and peripheral factors underlying GES-associated improvement of appetite we developed a GES model in anaesthetized Wistar rats. During laparotomy, two electrodes were implanted into the stomach and high-frequency low-energy GES (14 Hz, 5 mA) was applied. The effects of 1 h GES were compared with sham stimulation. After GES, c-Fos expression was increased in the mucosal and submucosal layers of the stimulated area (174%). In the stomach, GES increased ghrelin mRNA (178%) and doubled the number of ghrelin-positive cells, resulting in elevated plasma levels of ghrelin (2.3 ± 0.2 vs. 1.6 ± 0.2 ng/mL). In the arcuate nucleus of the hypothalamus, GES increased c-Fos (277%) and agouti-related protein (AgRP) mRNA expression (135%). GES reduced the number of c-Fos-positive cells throughout the nucleus of the solitary tract (between 93 and 75% from rostral to caudal levels) including catecholaminergic neurons (81% at caudal level). Gastric emptying, plasma glucose and heart rate variability were not affected by GES. This study shows that GES may improve appetite via stimulation of main orexigenic pathways, including ghrelin production in the stomach and AgRP in the hypothalamus, as well as by reducing the activity of catecholaminergic brainstem neurons.
Digestive System & Nutrition Laboratory (ADEN EA4311), Institute of Medical Research and Innovation, Rouen University & Hospital, IFR23, Rouen 76183, France.
Syrine
S
Gallas
Maria Hamze
MH
Sinno
Nabile
N
Boukhettala
Moïse
M
Coëffier
Nathalie
N
Dourmap
Guillaume
G
Gourcerol
Philippe
P
Ducrotté
Pierre
P
Déchelotte
Anne-Marie
AM
Leroi
Sergueï O
SO
Fetissov
D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000502:physiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D001786:Blood Glucose; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods*; D005746:Gastric Emptying / Q000502:physiology; D054439:Ghrelin / Q000096:biosynthesis* / Q000235:genetics; D006339:Heart Rate; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000033:anatomy & histology / Q000502:physiology*
D054369:Agouti-Related Protein; D001786:Blood Glucose; D002395:Catecholamines; D054439:Ghrelin; D016760:Proto-Oncogene Proteins c-fos