Avaliação do efeito transgeracional da indução a obesidade por dieta no Zebrafish (Danio Rerio)

Abstract

The present study aimed to investigate the effects of a high-carbohydrate diet on the induction of obesity in adult zebrafish across generations. To achieve this, animals of both sexes were used and, for twelve weeks, were divided into two groups based on the diet provided. The Control group was fed a balanced diet for the species, while the High Carbohydrate Diet (HCD) group received a high-carbohydrate diet. In the last week of the feeding protocol, the parental generation (P) animals underwent reproductive management. Specific sex crossings between parental groups were conducted to independently investigate maternal and paternal influences, resulting in four experimental groups in the F1 generation: F1C; F1HCD; F1P; and F1M. Upon reaching sexual maturity, each group was subdivided into two subgroups: one receiving the Control diet, while the other was subjected to HCD consumption. This resulted in eight groups in the adult F1 generation that underwent the same feeding protocol as the P generation. Finally, the groups were also subjected to reproductive management, leading to the production of the F2 generation, which was not subjected to intergroup crossings. To assess the impact of the diet on adult animals at the end of each feeding protocol, for both P and F1 generations, analysis of body weight, subcutaneous and visceral adipocyte morphometry, biochemical, and enzymatic analyses were performed. Additionally, transcriptional regulation of genes associated with feeding behavior, neuroinflammation, and epigenetics modifications was evaluated. Results from the P generation showed a significant increase in the body weight of HCD group animals from the fifth week onwards (p<0.05), inducing a condition similar to obesity in all analyzed parameters. Furthermore, these animals exhibited anxiety-like behavior, and alterations in the transcriptional regulation of genes associated with food consumption and inflammatory profile were identified. Male and female F1 generation descendants of obese parents subjected to HCD also showed changes in the regulation of genes related to neuroinflammation and epigenetics modifications. HCD consumption did not affect the reproductive capacity of the different groups analyzed in the P and F1 generations. However, alterations in inflammatory profiles and the activity of antioxidant enzymes were identified in the offspring of males and females that consumed HCD across generations. These findings provide unprecedented data for a better understanding of the transgenerational effects of obesity induced by high-carbohydrate diets in zebrafish.