Appetite regulating genes in zebrafish gut; a gene expression study

Abstract

The underlying molecular pathophysiology of feeding disorders, particularly in peripheral organs, is still largely unknown. A range of molecular factors encoded by appetite-regulating genes are already described to control feeding behaviour in the brain. However, the important role of the gastrointestinal tract in the regulation of appetite and feeding in connection to the brain has gained more attention in the recent years. An example of such inter-organ connection can be the signals mediated by leptin, a key regulator of body weight, food intake and metabolism, with conserved anorexigenic effects in vertebrates. Leptin signals functions through its receptor (lepr) in multiple organs, including the brain and the gastrointestinal tract. So far, the regulatory connections between leptin signal and other appetite-regulating genes remain unclear, particularly in the gastrointestinal system. In this study, we used a zebrafish mutant with impaired function of leptin receptor to explore gut expression patterns of appetite-regulating genes, under different feeding conditions (normal feeding, 7-day fasting, 2 and 6-hours refeeding). We provide evidence that most appetite-regulating genes are expressed in the zebrafish gut. On one hand, we did not observed significant differences in the expression of orexigenic genes (except for hcrt) after changes in the feeding condition. On the other hand, we found 8 anorexigenic genes in wild-types (cart2, cart3, dbi, oxt, nmu, nucb2a, pacap and pomc), as well as 4 genes in lepr mutants (cart3, kiss1, kiss1r and nucb2a), to be differentially expressed in the zebrafish gut after changes in feeding conditions. Most of these genes also showed significant differences in their expression between wild-type and lepr mutant. Finally, we observed that impaired leptin signalling influences potential regulatory connections between anorexigenic genes in zebrafish gut. Altogether, these transcriptional changes propose a potential role of leptin signal in the regulation of feeding through changes in expression of certain anorexigenic genes in the gastrointestinal tract of zebrafish.

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

“…The changes in the levels of ObRb in the cellular membrane depend on the synthesis, transport, internalization, and recycling, among other factors. These levels regulate the efficiency of leptin action and are known to increase after fasting and decrease after food intake, with leptin increasing hypothalamic expression of leptin receptor [ 163 ] but being unable to do so after the administration of diets rich in saturated fats. There are different molecules that regulate the exposure of ObRb in the cell membrane.…”