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

• Published in: The FASEB journal 2012-01, Vol.26 (1), p.259-271
• Main Authors: Kang, Kihwa, Schmahl, Jennifer, Lee, Jong‐Min, Garcia, Karen, Patil, Ketan, Chen, Amelia, Keene, Michelle, Murphy, Andrew, Sleeman, Mark W., Research, Center for Human Genetic
• Format: Article
• Language: English
• Subjects: Acylation; Acyltransferases - genetics; Acyltransferases - metabolism; Adipose Tissue - anatomy & histology; Adipose Tissue - metabolism; Animals; Bile Acids and Salts - metabolism; Biliary Tract - metabolism; Cell Line; Chromosomes, Artificial, Bacterial - genetics; Eating - physiology; Gallbladder - metabolism; Gene Expression Profiling; Ghrelin - metabolism; Ileum - metabolism; Intestinal Absorption - physiology; intestine; ISBT; Key Words; Lac Operon - genetics; Male; Metabolome - genetics; metabolomics; Mice; Mice, Mutant Strains; Pituitary Gland, Anterior - metabolism
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.11-191460

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.—Kang, K., Schmahl, J., Lee, J. ‐M., Garcia, K., Patil, K., Chen, A., Keene, M., Murphy, A., Sleeman, M. W. Mouse ghrelin‐O‐acyltransferase (GOAT) plays a critical role in bile acid reabsorption. FASEB J. 26, 259–271 (2012). www.fasebj.org