Impact of high-fat diet on lifespan, metabolism, fecundity and behavioral senescence in Drosophila

Excess consumption of high-fat diet (HFD) is likely to result in obesity and increases the predisposition to associated health disorders. Drosophila melanogaster has emerged as an important model to study the effects of HFD on metabolism, gut function, behavior, and ageing. In this study, we investigated the long-term effects of HFD on physiology and behavior of female flies. We found that HFD decreases lifespan, and also with age leads to accelerated decline of climbing ability and increased sleep fragmentation. Furthermore, long-term exposure to HFD results in elevated adipokinetic hormone (AKH) transcript levels and an increased crop with massive lipid stores. We detected no long-term effects of HFD on body mass, or levels of triacylglycerids, glycogen or glucose, although fecundity was diminished. Finally, we investigated the role of AKH and Drosophila insulin like peptides (DILPs) in regulating effects of HFD during aging. Both with normal diet (ND) and HFD, Akh mutant flies displayed increased longevity compared to control flies, both mutants and controls showed shortened lifespan on HFD compared to ND. Triple mutants of dilp2,3,5 are characterized by long lifespan on ND, but HFD drastically shortened longevity. Thus, long-term exposure to HFD impairs lifespan and fecundity and augments age-related behavioral senescence.