Assessing the role of ghrelin and the enzyme ghrelin O-acyltransferase (GOAT) system in food reward, food motivation, and binge eating behavior. (October 2021)

• Record Type: Journal Article
• Authors: Micioni Di Bonaventura, Emanuela; Botticelli, Luca; Del Bello, Fabio; Giorgioni, Gianfabio; Piergentili, Alessandro; Quaglia, Wilma; Cifani, Carlo; Micioni Di Bonaventura, Maria Vittoria
• Is Part Of: Pharmacological research. Volume 172(2021)
• Publication Date: 2021-10
• Subjects: D-AP5 (PubChem CID: 135342) -- JMV2959 (PubChem CID: 16114404) -- [D-Lys3]-GHRP-6 (PubChem CID: 5311279) -- SCH-23390 (PubChem CID: 5018) -- Eticlopride (PubChem CID: 57267) -- Exendin-4 (PubChem CID: 16157882) -- Ro60-0175 (PubChem CID: 3045227) -- Naltrexone (PubChem CID: 5360515) -- NorBNI (PubChem CID: 5480230) -- WIN55, 212-2 (PubChem CID: 5311501) -- Tetrahydrocannabinol (PubChem CID: 16078) -- Rimonabant (PubChem CID: 104850) -- LH-21 (PubChem CID: 10136173) -- SB-334867 (PubChem CID: 6604926); GHSR1a growth hormone secretagogue receptor type 1a -- GOAT ghrelin O-acyltransferase -- DAG des-acyl-ghrelin -- AG acyl-ghrelin -- HPA hypothalamic–pituitary–adrenal -- GH growth hormone -- GPCR G protein-coupled receptor -- ARC Arcuate nucleus of the hypothalamus -- VTA ventral tegmental area -- NTS Nucleus of the tractus solitarius -- NPY Neuropeptide Y -- AgRP Agouti-related peptide -- ICV intracerebroventricular -- POMC Pro-opiomelanocortin -- MC4R melanocortin-4 receptor -- PVN paraventricular nucleus of the hypothalamus -- HPF highly palatable foods -- BE binge eating -- BN Bulimia nervosa -- AN Anorexia nervosa -- BED Binge eating disorder -- NAc Nucleus accumbens -- PFC Prefrontal cortex -- CPP conditioned place preference -- NMDA N-methyl-D-aspartate -- HFD high-fat-diet -- KO knockout -- IP intraperitoneal -- GLP-1 glucagon-like peptide 1 -- 5-HT 5-hydroxytryptamine -- MOR mu-opioid receptor -- DOR delta-opioid receptor -- KOR kappa-opioid receptor -- shRNA short-hairpin RNAs -- AEA anandamide -- 2-AG 2-arachidonoylglycerol -- CB1R cannabinoid receptor type 1 -- CB2R cannabinoid receptor type 2 -- WT Wild type -- AMPK AMP-activated protein kinase activity -- OX1R orexin-1 receptor -- OX2R orexin-2 receptor -- LHA lateral hypothalamic area -- VHP ventral hippocampus -- MBOATs membrane-bound O-acyltransferases -- MCT medium-chain triglycerides -- HPA hypothalamic-pituitary-adrenal -- ACTH adrenocorticotropic hormone -- DAT-GHSR GHSR expression limited to dopamine neurons -- FAA food anticipatory activity -- fMRI functional magnetic resonance imaging -- BMI body mass index -- BES Binge Eating Scale -- TSST Trier Social Stress Test; Ghrelin -- Food reward -- Ghrelin O-acyltransferase (GOAT) -- Binge eating disorder (BED) -- Hypothalamic-pituitary-adrenal (HPA) axis -- Obesity; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105847
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: The peripheral peptide hormone ghrelin is a powerful stimulator of food intake, which leads to body weight gain and adiposity in both rodents and humans. The hormone, thus, increases the vulnerability to obesity and binge eating behavior. Several studies have revealed that ghrelin's functions are due to its interaction with the growth hormone secretagogue receptor type 1a (GHSR1a) in the hypothalamic area; besides, ghrelin also promotes the reinforcing properties of hedonic food, acting at extra-hypothalamic sites and interacting with dopaminergic, cannabinoid, opioid, and orexin signaling. The hormone is primarily present in two forms in the plasma and the enzyme ghrelin O-acyltransferase (GOAT) allows the acylation reaction which causes the transformation of des-acyl-ghrelin (DAG) to the active form acyl-ghrelin (AG). DAG has been demonstrated to show antagonist properties; it is metabolically active, and counteracts the effects of AG on glucose metabolism and lipolysis, and reduces food consumption, body weight, and hedonic feeding response. Both peptides seem to influence the hypothalamic–pituitary–adrenal (HPA) axis and the corticosterone/cortisol level that drive the urge to eat under stressful conditions. These findings suggest that DAG and inhibition of GOAT may be targets for obesity and bingeing-related eating disorders and that AG/DAG ratio may be an important potential biomarker to assess the risk of developing maladaptive eating behaviors. Graphical Abstract: ga1 Highlights: Ghrelin impacts food reward by increasing mesolimbic dopamine transmission. Ghrelin interacts with dopaminergic, cannabinoid, opioid, and orexin signaling. GOAT inhibition is a pharmacological tool to block the orexigenic effect of ghrelin. Ghrelin influences HPA axis activity and bingeing-related eating disorders. Ghrelin system dysregulation increases the risk of obesity and binge eating behavior.