Abstract
The signal mediated by leptin hormone and its receptor is a major regulator of body weight, food intake and metabolism. In mammals and many teleost fish species, leptin has an anorexigenic role and inhibits food intake by influencing the appetite centres in the hypothalamus. However, the regulatory connections between leptin and downstream genes mediating its appetite-regulating effects are still not fully explored in teleost fish. In this study, we used a loss of function leptin receptor zebrafish mutant and real-time quantitative PCR to assess brain expression patterns of several previously identified anorexigenic genes downstream of leptin signal under different feeding conditions (normal feeding, 7-day fasting, 2 and 6-h refeeding). These downstream factors include members of cart genes, crhb and gnrh2, as well as selected genes co-expressed with them based on a zebrafish co-expression database. Here, we found a potential gene expression network (GRN) comprising the abovementioned genes by a stepwise approach of identifying co-expression modules and predicting their upstream regulators. Among the transcription factors (TFs) predicted as potential upstream regulators of this GRN, we found expression pattern of sp3a to be correlated with transcriptional changes of the downstream gene network. Interestingly, the expression and transcriptional activity of Sp3 orthologous gene in mammals have already been implicated to be under the influence of leptin signal. These findings suggest a potentially conserved regulatory connection between leptin and sp3a, which is predicted to act as a transcriptional driver of a downstream gene network in the zebrafish brain.
Highlights
Feeding behaviour is controlled by processes involving appetitive behaviours1 3 Vol.:(0123456789)and food ingestion (Keen-Rhinehart et al 2013)
We aimed to investigate the existence of potential gene expression network (GRN)(s) containing cart, crh and gnrh2 genes, which can be controlled by leptin signal in zebrafish brain under different feeding conditions
We demonstrated that fasting reduces the expression of all the cart genes in the brain and their expression reduction maintains during short-term refeeding period (i.e. 2 h and 6 h after refeeding)
Summary
Feeding behaviour is controlled by processes involving appetitive behaviours (hunger-driven activities)1 3 Vol.:(0123456789)and food ingestion (Keen-Rhinehart et al 2013). The neurons mediating the appetite-regulating effects, so called accurate nucleus neurons in mammals (Opazo et al 2019), are located in the periventricular and lateral parts of the hypothalamus in fish (Jeong et al 2018) These neurons can be classified into two main types: orexigenic, stimulating food intake and/or locomotor activity, and anorexigenic, reducing food intake and/or locomotor activity (Sohn 2015). The appetite-regulation genes are the major player in these processes, and to this date, a range of neuropeptides and their cognate receptors encoded by these genes are identified in fish (Volkoff 2016) These genes can be categorised based on their orexigenic and anorexigenic functions (Arora and Anubhuti 2006; Parker and Bloom 2012). Despite recent advances in understanding the functions of these genes in controlling appetite, little is known about their transcriptional regulatory connections under different feeding conditions in fish
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
