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..

Lmx1a functions in intestinal serotonin-producing enterochromaffin cells downstream of Nkx2.2

“…Consistent with the increase in Ghrl + cells, there was elevated expression of membrane bound O-acyltransferase domain containing 4 (Mboat4), the enzyme that is co-expressed with Ghrl and converts the Ghrl peptide to its biologically active, acylated form (Gutierrez et al, 2008(Gutierrez et al, , 2012Kang et al, 2012) (Table 2).…”

MECHANISMS IN ENDOCRINOLOGY: Ghrelin: the differences between acyl- and des-acyl ghrelin

“…AG is produced mainly by the stomach and exerts its central and peripheral effects through GHSR1a (1). The ghrelin peptide is acylated by the enzyme ghrelin O-acyl transferase (GOAT) (3,4,5), which is expressed predominantly in the stomach, gut, and pancreas but also at other sites (6).…”

Ghrelin O-acyltransferase (GOAT) and energy metabolism

“…In 2012, a metabolomics analysis of plasma samples and gene expression analysis of tissues taken from GOAT / mice highlighted significant changes in bile acid metabolites and relevant transporters (Kang et al, 2012). Serum metabolite profile analysis revealed secondary bile acids are increased by more than 2.5-fold in GOAT / mice.…”

“…This effect was attributed to increased expression of the ileal sodium-dependent bile acid transporter in the intestinal and biliary tract. Further, a number of up-regulated solute carrier family genes were identified by microarray analysis of the intestinal tract of GOAT / mice (Kang et al, 2012). Among these was Slc5a12.…”