Abstract
Ghrelin O-acyltransferase (GOAT), a member of MBOATs family, is essential for octanoylation of ghrelin, which is required for active ghrelin to bind with and activate its receptor. GOAT is expressed mainly in the stomach, pancreas and hypothalamus. Levels of GOAT are altered by energy status. GOAT contains 11 transmembrane helices and one reentrant loop. Its invariant residue His-338 and conserved Asn-307 are located in the endoplasmic reticulum lumen and cytosol respectively. GOAT contributes to the regulation of food intake and energy expenditure, as well as glucose and lipids homeostasis. Deletion of GOAT blocks the acylation of ghrelin leading to subsequent impairment in energy homeostasis and survival when mice are challenged with high energy diet or severe caloric restriction. GO-CoA-Tat, a peptide GOAT inhibitor, attenuates acyl-ghrelin production and prevents weight gain induced by a medium-chain triglycerides-rich high fat diet. Further, GO-CoA-Tat increases glucose- induced insulin secretion. Overall, inhibition of GOAT is a novel strategy for treatment of obesity and related metabolic disorders.
Highlights
Ghrelin is the only circulating hormone that exhibits potent stimulation of food intake
Search for the octanoylation catalytic enzyme led to the discovery of ghrelin O-acyltransferase (GOAT)
All GOAT constructs resulted in successful octanoylation of human ghrelin, indicating that the function of GOAT is highly conserved across vertebrate species (Gutierrez et al, 2008)
Summary
Received August 17, 2015; received October 9, 2015; published online January 4, 2016. Ghrelin O-acyltransferase (GOAT), a member of MBOATs family, is essential for octanoylation of ghrelin, which is required for active ghrelin to bind with and activate its receptor. Levels of GOAT are altered by energy status. GOAT contributes to the regulation of food intake and energy expenditure, as well as glucose and lipids homeostasis. Deletion of GOAT blocks the acylation of ghrelin leading to subsequent impairment in energy homeostasis and survival when mice are challenged with high energy diet or severe caloric restriction. GO-CoA-Tat, a peptide GOAT inhibitor, attenuates acyl-ghrelin production and prevents weight gain induced by a medium-chain triglycerides-rich high fat diet. Inhibition of GOAT is a novel strategy for treatment of obesity and related metabolic disorders. Ghrelin O-acyltransferase (GOAT), acyl-ghrelin, enzyme inhibitor, food intake, energy metabolism, obesity
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