Mouse ghrelin-O-acyltransferase (GOAT) plays a critical role in bile acid reabsorption

Kihwa Kang, Jennifer Schmahl, Jong-Min Lee, Karen Garcia, Ketan Patil, Amelia Chen, Michelle Keene, Andrew J Murphy, Mark W Sleeman

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

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..
Original languageEnglish
Pages (from-to)259 - 271
Number of pages13
JournalThe FASEB Journal
Volume26
Issue number1
DOIs
Publication statusPublished - 2012
Externally publishedYes

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