title: Ghrelin O-acyltransferase (GOAT) and energy metabolism.
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.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA.
authors.forename: Ziru
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA. micham@umich.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Mulholland
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA. weizhenz@umich.edu.|Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, China. weizhenz@umich.edu.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004435:Eating / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D009765:Obesity / Q000201:enzymology*; D014018:Tissue Distribution
chemical_list: D054439:Ghrelin; D000217:Acyltransferases
keywords: acyl-ghrelin; energy metabolism; enzyme inhibitor; food intake; ghrelin O-acyltransferase (GOAT); obesity