Mammalian ghrelin is a stomach-derived peptide that stimulates secretion of growth hormone and food intake. Zebrafish is an excellent model system for forward genetic studies, and many aspects of energy homeostasis characterized in mammals appear to be conserved in the zebrafish. In this study, we investigated the expression and regulation of zebrafish ghrelin by metabolic status. Quantitative RT-PCR revealed that zebrafish ghrelin is highly enriched in anterior gut associated tissues. Using in situ hybridization with adult zebrafish tissues, we found that zebrafish ghrelin mRNA was not expressed in intestine tissue, but rather in clusters of endocrine pancreas cells distinct from insulin-expressing islets. Fasting specifically upregulated pancreatic ghrelin but not brain ghrelin expression by 3- to 4-fold and refeeding restored ghrelin transcript to control levels seen in the fed group within 5 h. These results demonstrate that although ghrelin is expressed in a different site in zebrafish, it is responsive to metabolic state in a similar manner as mammalian ghrelin, suggesting a role in the regulation of feeding in teleosts, and thus validate the utility of zebrafish as a genetic model system for the analysis of the ghrelin system and energy homeostasis. (C) 2013 Elsevier Inc. All rights reserved.