Possible role of transcription factors (BSX, NKX2.1, IRX3 and SIRT1) in the regulation of appetite in goldfish (Carassius auratus)

The homeobox genes play important roles in the embryonic development of animals. Recent evidence suggests they might also regulate feeding and act as transcription factors of appetite regulators. Examples of these genes are a brain-specific homeobox transcription factor (BSX), NK2 homeobox 1 (NKX2.1) and the Iroquois homeobox 3 (IRX3). Sirtuin1 (SIRT1) acts as a transcription factor for nutrient (e.g. lipid, glucose) homeostasis and responds to stress and nutrient availability, and has been shown to interact with appetite regulators. Very little is known about the role of these genes in the regulation of feeding and nutrient homeostasis in fish. In this study, we assessed the roles of BSX, NKX2.1, IRX3 and SIRT1 in the central regulation of feeding in goldfish by examining their mRNA brain distribution, assessing the effects of fasting on their brain expression and assessing the effects of peripheral injections of cholecystokinin (CCK, a brain-gut peptide), on their brain expression. All genes showed a widespread distribution in the brain, with high levels in the hypothalamus. In both hypothalamus and telencephalon, fasting induced increases in BSX, IRX3 and NKX2.1 expressions but had no effect on SIRT1 expression levels. CCK injections increased hypothalamic expression levels of IRX3 and SIRT1, and telencephalic expression levels of NKX2.1 and SIRT1, with no effect on either hypothalamic BSX or NKX2.1 expression levels or telencephalon BSX or IRX3 expression levels. Our results suggest that, in goldfish as in mammals, central BSX, NKX2.1, IRX3 and SIRT1 are present in regions of the brain regulating feeding, are sensitive to nutrient status and interact with appetite-regulating peptides.