Xenin is a novel anorexigen in goldfish (<i>Carassius auratus</i>)

<div><p>Xenin, a highly conserved 25 amino acid peptide cleaved from the N-terminus of the coatomer protein alpha (COPA), is emerging as a food intake regulator in mammals and birds. To date, no research has been conducted on xenin biology in fish. This study aims to identify the <i>copa</i> mRNA encoding xenin in goldfish (<i>Carassius auratus</i>) as a model, to elucidate its regulation by feeding, and to describe the role of xenin on appetite. First, a partial sequence of <i>copa</i> cDNA, a region encoding xenin, was identified from goldfish brain. This sequence is highly conserved among both vertebrates and invertebrates. RT-qPCR revealed that <i>copa</i> mRNAs are widely distributed in goldfish tissues, with the highest levels detected in the brain, gill, pituitary and J-loop. Immunohistochemistry confirmed also the presence of COPA peptide in the hypothalamus and enteroendocrine cells on the J-loop mucosa. In line with its anorexigenic effects, we found important periprandial fluctuations in <i>copa</i> mRNA expression in the hypothalamus, which were mainly characterized by a gradually decrease in <i>copa</i> mRNA levels as the feeding time was approached, and a gradual increase after feeding. Additionally, fasting differently modulated the expression of <i>copa</i> mRNA in a tissue-dependent manner. Peripheral and central injections of xenin reduce food intake in goldfish. This research provides the first report of xenin in fish, and shows that this peptide is a novel anorexigen in goldfish.</p>