title: Mouse ghrelin-O-acyltransferase (GOAT) plays a critical role in bile acid reabsorption.
abstract: Ghrelin is a unique peptide gut hormone that requires post-translational modification to stimulate both feeding and growth hormone release. Ghrelin O-acyltransferase (GOAT) was identified as a specific acyl-transferase for ghrelin, and recent genetic deletion studies of the Goat gene (Goat(-/-)) uncovered the role of ghrelin in the regulation of glucose homeostasis. To further understand the physiological functions of the GOAT/ghrelin system, we have conducted a metabolomic and microarray profile of Goat-null mice, as well as determined Goat expression in different tissues using the lacZ reporter gene. Serum metabolite profile analysis revealed that Goat(-/-) mice exhibited increased secondary bile acids >2.5-fold. This was attributed to increased mRNA and protein expression of the ileal sodium-dependent bile acid transporter (ISBT) in the intestinal and biliary tract. Increased expression of additional solute carrier proteins, including Slc5a12 (>10-fold) were also detected in the small intestine and bile duct. Goat staining was consistently observed in the pituitary glands, stomach, and intestines, and to a lesser extent in the gallbladder and pancreatic duct. This is the first report that the GOAT/ghrelin system regulates bile acid metabolism, and these findings suggest a novel function of GOAT in the regulation of intestinal bile acid reabsorption..
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY, USA. kihwa.kang@regeneron.com
authors.forename: Kihwa
authors.initials: K
authors.lastname: Kang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schmahl
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Karen
authors.initials: K
authors.lastname: Garcia
authors.forename: Ketan
authors.initials: K
authors.lastname: Patil
authors.forename: Amelia
authors.initials: A
authors.lastname: Chen
authors.forename: Michelle
authors.initials: M
authors.lastname: Keene
authors.forename: Andrew
authors.initials: A
authors.lastname: Murphy
authors.forename: Mark W
authors.initials: MW
authors.lastname: Sleeman
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism*; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001659:Biliary Tract / Q000378:metabolism; D002460:Cell Line; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D004435:Eating / Q000502:physiology; D005704:Gallbladder / Q000378:metabolism; D020869:Gene Expression Profiling; D054439:Ghrelin / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology*; D007763:Lac Operon / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D055442:Metabolome / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D010903:Pituitary Gland, Anterior / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D054439:Ghrelin; D008565:Membrane Proteins; D000217:Acyltransferases; C526983:Mboat4 protein, mouse