Food intake and appetite control in a GH-transgenic zebrafish

Abstract

The biological actions of growth hormone (GH) are pleiotropic, including growth promotion, energy mobilization, gonadal development, appetite, and social behavior. The regulatory network for GH is complex and includes many central and peripheral endocrine factors as well as that from the environment. It is known that GH transgenesis results in increased growth, food intake, and consequent metabolic rates in fishes. However, the manner in which GH transgenesis alters the energetic metabolism in fishes has not been well explored. In order to elucidate these consequences, we examined the effect of GH overexpression on appetite control mechanisms in a transgenic zebrafish (Danio rerio) model. To this, we analyzed feeding behavior and the expression of the main appetite-related genes in two different feeding periods (fed and fasting) in non-transgenic (NT) and transgenic (T) zebrafish as well as glycaemic parameters of them. Our initial results have shown that NT males and females present the same feeding behavior and expression of main appetite-controlling genes; therefore, the data of both sexes were properly grouped. Following grouped data analyses, we compared the same parameters in NT and T animals. Feeding behavior results have shown that T animals eat significantly more and faster than NT siblings. Gene expression results pointed out that gastrointestinal (GT) cholecystokinin has a substantial contribution to the communication between peripheral and central control of food intake. Brain genes expression analyses revealed that T animals have a down-regulation of two strong and opposite peptides related to food intake: the anorexigenic proopiomelanocortin (pomc) and the orexigenic neuropeptide Y (npy). The down-regulation of pomc in T when compared with NT is an expected result, since the decrease in an anorexigenic factor might keep the transgenic fish hungry. The down-regulation of npy seemed to be contradictory at first, but if we consider the GH's capacity to elevate blood glucose, and that NPY is able to respond to humoral factors like glucose, this down-regulation makes sense. In fact, our last experiment showed that transgenics presented elevated blood glucose levels, confirming that npy might responded to this humoral factor. In conclusion, we have shown that GT responds to feeding status without interference of transgenesis, whereas brain responds to GH transgenesis without any effect of treatment. It is clear that transgenic zebrafish eat more and faster, and it seems that it occurs due to pomc down-regulation, since npy might be under regulation of the humoral factor glucose.

The Neuroendocrine Regulation of Food Intake in Fish: A Review of Current Knowledge

“…In zebrafish larvae, although early ISH studies could not detect fasting-induced changes in hypothalamic POMC transcript levels (Song et al, 2003), more recent qPCR studies indicate that POMCa expression decreases in starved fish (Shanshan et al, 2016). In addition, GH-transgenic zebrafish, who have increased feeding, display down-regulation of POMC (Dalmolin et al, 2015), consistent with an anorexigenic role for POMC-derived peptides in Cypriniformes.…”

Central regulation of food intake in fish: an evolutionary perspective

“…In mammals, the α-melanocyte-stimulating hormone (α-MSH, product of POMC) is an anorexigenic peptide that activates MC4R resulting in food intake inhibition (Loh et al 2015), while the antagonism of this receptor by AgRP exerts orexigenic actions (Rui 2013, Sohn 2015, Takeuchi 2016. Studies in cyprinids and salmonids (Kojima et al 2010, Zhang et al 2012, Dalmolin et al 2015, Guillot et al 2016 suggest that AgRP would counteract the basal inhibition of feeding induced by the melanocortin system (Kojima et al 2010, Zhang et al 2012, Dalmolin et al 2015, Guillot et al 2016.…”

Appetite-Controlling Endocrine Systems in Teleosts

“…GH transgenesis, which results in increased feeding rates, does not affect brain npy levels in Coho salmon (36) and carp (37) but decreases npy levels in zebrafish (38). …”