The ancestral western diet causes transgenerational increase in offspring feeding behavior with parallel alterations in brain mitochondrial proteome and miRNAs.

Childhood obesity traces its roots to the parental lifestyle and eating habits. Familial clustering of obesity indicates that children’s feeding behavior is a result of a complex interplay between cultural inheritance, genetics, and epigenetics. In the current study, we asked a question if epigenetic factors, such as ancestral diet, could program offspring feeding behavior in a fruit fly model. Here we show that ancestral caloric overload produces a generational shift in the offspring’s feeding behavior, with a concomitant alteration in activity, triglycerides, and brain mitochondrial density. Mechanistically, we find the generational changes to be associated with alterations in brain mitochondrial proteome and miRNAs. The findings identify ancestral nutrition as a critical factor in the generational programming of feeding behavior.