Zebrafish larvae present noncoding RNAs linking anxiety with metabolic disorder

Human and rodent studies demonstrate an association between metabolic- and anxiety-related disorders. However, the biological pathways and age onset underlying the correlation between these two disorder types are largely unknown. Both short microRNAs (miRs) and long non-coding RNAs (lncRNAs) have been shown to take part in each disorder and are expressed throughout life in diverse organisms. Therefore, we hypothesized that the link between anxiety and metabolic-related disorders is based on noncoding RNAs (ncRNAs) and is initiated early in development. To challenge this hypothesis, we generated two zebrafish models, one of anxiety-like behavior and the other of obesity. Anxiety-like behavior, induced in larvae by a short-termed exposure to caffeine, was assessed by measuring erratic swimming and thigmotaxis, as well as whole body cortisol levels. Obesity, achieved by the addition of chicken egg yolk solution to the larval diet, was confirmed histologically according to the number and size of adipocytes per larva. To pursue ncRNAs which were differentially expressed in both models, RNA extracted from sample sets was subjected to short and long RNA-sequencing followed by bioinformatic analysis. The results point towards ncRNAs involved in pathways that link both anxiety and obesity. Taken together, our findings demonstrate that the links between anxiety and obesity extend to zebrafish larvae and reflect evolutionarily conserved regulatory pathways.