LAUSR

The purpose of this study is to assess the effects of early high-carbohydrate stimulus on glucose metabolism in zebrafish (Danio rerio) over two generations and explore the mechanisms that explain those nutritional programming effects via epigenetic modifications. The larvae were delivered a high-carbohydrate diet (53.66%) that was used as an early nutritional stimulus from the first feeding to the end of the yolk sac (FF) and 5 days after yolk-sac exhaustion (YE). The larvae (F0) and their offspring (F1) were then both fed the control diet (22.69%) until adulthood (15 weeks), and they were challenged with a high-carbohydrate diet (35.36%) at the 16th week. The results indicated that early stimulus immediately raised the mRNA levels of genes involved in glycolysis and gluconeogenesis. At the end of F0 challenge, both treatment groups decreased the plasma glucose levels, increased the expression levels of glucokinase (gck), and inhibited the mRNA during gluconeogenesis. When challenged in F1, the glucose levels were lower in FF (F1), and the mRNA levels of phosphoenolpyruvate carboxykinase 1 (pck1) were decreased in FF (F1) and YE (F1). Besides, in both experimental groups (F0 and F1), the CpG island of pck1 maintained lower levels of hypermethylated expression from F0 adult, 24 h post-fertilization embryo, to F1 adult. In conclusion, these results indicated that an early high-carbohydrate stimulus could significantly reprogram glucose metabolism in adult zebrafish, that those modifications could be partially transmitted to the next generation, and that the DNA methylation of pck1 might work as a stable epigenetic marker to contribute to those processes.