Paternal Western diet causes transgenerational increase in food consumption in Drosophila with parallel alterations in the offspring brain proteome and microRNAs

Several lines of evidence indicate that ancestral diet might play an important role in determining offspring's metabolic traits. However, it is not yet clear whether ancestral diet can affect offspring's food choices and feeding behavior. In the current study, taking advantage of Drosophila model system, we demonstrate that paternal Western diet (WD) increases offspring food consumption up to the fourth generation. Paternal WD also induced alterations in F1 offspring brain proteome. Using enrichment analyses of pathways for upregulated and downregulated proteins, we found that upregulated proteins had significant enrichments in terms related to translation and translation factors, whereas downregulated proteins displayed enrichments in small molecule metabolic processes, TCA cycles, and electron transport chain (ETC). Using MIENTURNET miRNA prediction tool, dme-miR-10-3p was identified as the top conserved miRNA predicted to target proteins regulated by ancestral diet. RNAi-based knockdown of miR-10 in the brain significantly increased food consumption, implicating miR-10 as a potential factor in programming feeding behavior. Together, these findings suggest that ancestral nutrition may influence offspring feeding behavior through alterations in miRNAs.

Automated summary

Multiple lines of evidence suggest that ancestral diet plays a crucial role in determining the metabolic traits of offspring. However, its impact on offspring's food choices and feeding behavior remains unclear. Using a Drosophila model system, this study demonstrates that a paternal Western diet (WD) increases food consumption in offspring up to the fourth generation and induces alterations in brain proteome. Further analysis reveals that the upregulated proteins are associated with translation and translation factors, while the downregulated proteins are related to small molecule metabolic processes, TCA cycles, and electron transport chain (ETC). The identification of miR-10 as a potential factor in programming feeding behavior suggests that ancestral nutrition may influence offspring's feeding behavior through alterations in miRNAs.