Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin and LEAP 2, in a 4‐day binge eating model

Abstract The growth hormone secretagogue receptor (GHSR) is a G protein‐coupled receptor that is highly expressed in the central nervous system.GHSRacts as a receptor for ghrelin and for liver‐expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin‐evoked activity.GHSRalso displays ligand‐independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced byLEAP2.GHSRactivity modulates a variety of food intake‐related behaviours, including binge eating. Previously, we reported thatGHSR‐deficient mice daily and time‐limited exposed to a high‐fat (HF) diet display an attenuated binge‐likeHFintake compared to wild‐type mice. In the present study, we aimed to determine whether ligand‐independentGHSRactivity affects binge‐likeHFintake in a 4‐day binge‐like eating protocol. We found that plasma levels of ghrelin andLEAP2 were not modified in mice exposed to this binge‐like eating protocol. Moreover, systemic administration of ghrelin orLEAP2 did not alterHFintake in our experimental conditions. Interestingly, we found that central administration ofLEAP2 or K‐(D‐1‐Nal)‐FwLL‐NH2, which are both blockers of constitutiveGHSRactivity, reduced binge‐likeHFintake, whereas central administration of ghrelin or the ghrelin‐evokedGHSRactivity blockers [D‐Lys3]‐GHRP‐6 andJMV2959 did not modify binge‐likeHFintake. Taken together, current data indicate thatGHSRactivity in the brain affects binge‐likeHFintake in mice independently of plasma levels of ghrelin andLEAP2.