Food intake and interdigestive gastrointestinal motility in ghrelin receptor mutant rats

Ghrelin is a gastric peptide hormone, discovered as being the endogenous ligand of growth hormone secretagogue receptor. Ghrelin is a 28 amino acid peptide presenting a unique n-octanoylation modification on its serine in position 3, catalyzed by ghrelin O-acyl transferase. Ghrelin is mainly produced by a subset of stomach cells and also by the hypothalamus, the pituitary, and other tissues. Transcriptional, translational, and posttranslational processes generate ghrelin and ghrelin-related peptides. Homo- and heterodimers of growth hormone secretagogue receptor, and as yet unidentified receptors, are assumed to mediate the biological effects of acyl ghrelin and desacyl ghrelin, respectively. Ghrelin exerts wide physiological actions throughout the body, including growth hormone secretion, appetite and food intake, gastric secretion and gastrointestinal motility, glucose homeostasis, cardiovascular functions, anti-inflammatory functions, reproductive functions, and bone formation. This review focuses on presenting the current understanding of ghrelin and growth hormone secretagogue receptor biology, as well as the main physiological effects of ghrelin.

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“…However, a contradictory study showed no effect of ghrelin on the migrating motor complex in mice [271]. …”

Section: Physiological Functionsmentioning

confidence: 99%

Structure and Physiological Actions of Ghrelin

2013

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“…Recently a GHSR-KO strain was developed at the Medical College of Wisconsin via the introduction of a point mutation in the GHSR gene of Fawn Hooded Hypertensive (FHH) rats (PhysGen Program in Genomic Application, http://pga.mcw.edu). As expected, GHSR-KO rats do not overeat in response to systemic ghrelin injections (Bülbül et al, 2011). Although this model is relatively new, studies show that compared to WT rats, GHSR-KO rats are less sensitive to the effects of cocaine as well as brain reward stimulation Wellman et al, 2012).…”

Section: Studying Ghrelinsupporting

confidence: 60%

“…54! (Bülbül et al, 2011;Cahill et al, 2014;Clifford et al, 2011) and was also not observed in Experiment 1A (testing day).…”

Section: Discussionmentioning

confidence: 65%

The Role of Ghrelin in Reward-Based Feeding

St-Onge¹

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The incidence of obesity has nearly doubled in the last 30 years, and this rise in incidence is directly linked to increased consumption of energy-dense foods. In addition, the majority of people attempting to lose weight report relapse to high fat foods while dieting. Recent studies suggest that the orexigenic hormone ghrelin can bind to dopaminergic cells in the ventral tegmental area (VTA), a key structure in the brain's reward system, and increase the incentive value of such foods. Specifically, studies have shown that ghrelin increases the motivation to work for food rewards, enhances the preference for contexts associated with food rewards, and augments the locomotor and physiological responses associated with food rewards. The experiments described in the present thesis aimed to establish the role of ghrelin in 2 additional reward-based feeding behaviours thought to contribute to the current obesity epidemic. The first behaviour is the consumption of palatable desserts after meals that adequately satisfy an individual's energetic demands. The second behaviour is the tendency to relapse to food seeking after a period of abstinence. In order to accomplish this, we compared ghrelin receptor knock out (KO) rats to rats possessing an identical genetic background, with an intact ghrelin receptor gene (wildtype rats -WT) in tasks designed to model these behaviours. In addition, we examined outbred rats receiving chronic infusions of either ghrelin or a ghrelin receptor antagonist in the VTA. Overall, the data presented in this thesis confirmed the role of ghrelin signalling in dessert consumption; KO rats ate less cookie dough when sated than WT rats. KO and WT rats performed similarly in operant conditioning and conditioned place preference models of relapse, also known as the operant and CPP reinstatement tests. In contrast, pharmacological action at the ghrelin ! iii! receptor in outbred rats could enhance and attenuate the expression of reinstatement of food seeking that is induced by food reward cues following administration of ghrelin and a ghrelin receptor antagonist, respectively. It is therefore likely that ghrelin is involved in the tendency to relapse to unhealthy eating habits in dieting individuals, and that this effect is due, in part, to its action in the reward system, particularly within the VTA. ! iv!

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“…2008). The intact GHSR structure is essential for the ghrelin‐dependent regulation of interdigestive motility and feeding behaviour (Bülbül et al . 2011; Yang et al .…”

Section: Discussionmentioning

confidence: 99%

The stimulating effect of ghrelin on gastric motility and firing activity of gastric‐distension‐sensitive hippocampal neurons and its underlying regulation by the hypothalamus

Luo

Gong

Wang

et al. 2013

Experimental Physiology

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New Findings r What is the central question of this study?Is there a direct pathway of ghrelin from the hypothalamic arcuate nucleus to the hippocampus? Is this pathway involved in the regulation of gastric motility and gastric afferent signalling? r What is the main finding and its importance?There exists a direct pathway of ghrelin from the hypothalamic arcuate nucleus to the hippocampus that is involved in the regulation of gastric motility. In the emotional hub hippocampus, ghrelin is involved in the regulation of gastric motility and gastric afferent signalling. These effects can be regulated by the hypothalamic arcuate nucleus. This supports and advances the theory of energy balance involving the regulation of the central and brain-gut peptides.Ghrelin is an acylated peptide originally identified in the rat stomach as the endogenous ligand for growth hormone secretagogue receptor (GHSR) that promotes gastric motility. Our aims were to explore the effects of ghrelin on gastric-distension-sensitive neurons in the hippocampus and the potential for ghrelin to regulate gastric motility through the arcuate nucleus (Arc). Single-unit discharges in the hippocampus were recorded extracellularly, and gastric motility in conscious rats was monitored. The expression of GHSR-1a in the hippocampus was determined by PCR, Western blot and fluo-immunohistochemistry staining. Retrograde tracing and fluoimmunohistochemistry staining were used to determine ghrelin neuron projection. GhrelinFluoro-Gold double-labelled neurons and GHSR-1a expression were observed in the Arc and hippocampus, respectively. There were gastric-distension-sensitive neurons in the hippocampus that could be excited by ghrelin or by electrical stimulation of the Arc. The excitatory effects could be blocked completely or partly by pretreatment with the ghrelin receptor antagonist [d-Lys-3]-GHRP-6. Gastric motility was significantly promoted by the administration of ghrelin into the hippocampus in a dose-dependent manner that could be completely abolished by [d-Lys-3]-GHRP-6. Electrical stimulation of the Arc could promote gastric motility as well. Nevertheless, these effects could be mitigated by pretreatment with [d-Lys-3]-GHRP-6. Electrical lesioning of the hippocampus diminished the excitatory effects on gastric motility that were induced by electrical stimulation the Arc. Our findings suggest that ghrelin plays an important role in

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Food intake and interdigestive gastrointestinal motility in ghrelin receptor mutant rats

Cited by 24 publications

References 39 publications

Structure and Physiological Actions of Ghrelin

Structure and Physiological Actions of Ghrelin

The Role of Ghrelin in Reward-Based Feeding

The stimulating effect of ghrelin on gastric motility and firing activity of gastric‐distension‐sensitive hippocampal neurons and its underlying regulation by the hypothalamus

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