RGD Reference Report - Rats with a truncated ghrelin receptor (GHSR) do not respond to ghrelin, and show reduced intake of palatable, high-calorie food. - Rat Genome Database

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Rats with a truncated ghrelin receptor (GHSR) do not respond to ghrelin, and show reduced intake of palatable, high-calorie food.

Authors: MacKay, Harry  Charbonneau, Valerie R  St-Onge, Veronique  Murray, Emma  Watts, Alexander  Wellman, Martin K  Abizaid, Alfonso 
Citation: MacKay H, etal., Physiol Behav. 2016 Sep 1;163:88-96. doi: 10.1016/j.physbeh.2016.04.048. Epub 2016 Apr 27.
RGD ID: 150520013
Pubmed: PMID:27129673   (View Abstract at PubMed)
DOI: DOI:10.1016/j.physbeh.2016.04.048   (Journal Full-text)

Ghrelin, a peptide hormone produced by the stomach, is the endogenous ligand for the Growth Hormone Secretagogue Receptor (GHSR). Ghrelin acts on the GHSR to increase food intake, appetitive behaviors, and adiposity. Recently, a rat model with a null mutation to the GHSR gene (FHH-GHSR(m1/Mcwi)) was generated and used in behavioral studies, but the basic metabolic phenotype of this strain as well as that of the background strain (Fawn Hooded Hypertensive, FHH) has not been characterized in detail. Here we compared male FHH-GHSR(m1/Mcwi) rats with their wild-type littermates (FHH-WT) in a number of metabolic parameters. In the 24h of recovery following an acute overnight fast, FHH-GHSR(m1/Mcwi) rats consumed less food than FHH-WT animals, and relative to their body weights, adult FHH-GHSR(m1/Mcwi) rats consumed fewer calories when placed on a high-fat diet. Despite this, FHH-GHSR(m1/Mcwi) rats did not show a difference in diet-induced obesity or weight gain. Fasted FHH-GHSR(m1/Mcwi) rats exhibited increased Agouti-Related Peptide (AgRP) and Neuropeptide Y (NPY) expression in the Arcuate Nucleus (ARC), indicative of altered central regulation of feeding and energy balance. FHH-GHSR(m1/Mcwi) rats exhibited lower levels of home cage locomotor behavior over the entire light/dark cycle, and reduced levels of food anticipatory activity when placed on a restricted feeding schedule. Finally, FHH-GHSR(m1/Mcwi) rats consumed less of a palatable dessert (cookie dough) given after the completion of the scheduled meal. Altogether, our data show that rats lacking a functional GHSR tend to eat less than their wild-type counterparts in the face of acute fasts, chronic high-fat diet exposure, and exposure to a palatable dessert, despite not showing differences in body weight and glucose homeostasis that are characteristic of GHSR null mice. These data indicate that many, but not all responses to GHSR ablation are conserved between rats and mice. The FHH-GHSR(m1/Mcwi) rat thus represents a novel and useful model for studying GHSR function in rats.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FHH-Ghsrm1McwiRatabnormal locomotor behavior  IMP compared to wild type ratsRGD 
GhsrRatabnormal locomotor behavior  IMP DNA:missense mutation:cds:nucleotide 1027RGD 
Ghsrm1McwiRatabnormal locomotor behavior  IMP compared to wild type ratsRGD 
FHH-Ghsrm1McwiRatdecreased circulating growth hormone level  IMP compared to wild type rats in response to ghrelin CHEBI:75431RGD 
GhsrRatdecreased circulating growth hormone level  IMP DNA:missense mutation:cds:nucleotide 1027RGD 
Ghsrm1McwiRatdecreased circulating growth hormone level  IMP compared to wild type rats in response to ghrelin CHEBI:75431RGD 
FHH-Ghsrm1McwiRatdecreased food intake  IMP compared to wild type ratsRGD 
GhsrRatdecreased food intake  IMP DNA:missense mutation:cds:nucleotide 1027RGD 
Ghsrm1McwiRatdecreased food intake  IMP compared to wild type ratsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Ghsr  (growth hormone secretagogue receptor)
Ghsrm1Mcwi  (growth hormone secretagogue receptor; mutation 1, Medical College of Wisconsin)

Strains
FHH-Ghsrm1Mcwi  (NA)


Additional Information