Maternal Nutritional Influence on Progeny Physiology, Longevity, and Immune System in <em>Drosophila melanogaster</em>

Abstract

Maternal obesity can influence the health of offspring through immunity, epigenetic regulations, telomeres length and development of gut dysbiosis, cancer, diabetes and brain disorders, which may also affect the long term and result in diminished life expectancy. Drosophila melanogaster is a practical model for investigating the role of maternal diet in descendants. The primary immune cells of invertebrates are named hemocytes, and the majority of hemocytes consist of plasmatocytes, which are macrophage-like cells. Genetic, epigenetic, or non-optimal maternal circumstances can cause the hemocytes of descendants to adapt and reprogram their development in Drosophila, resulting in long-term influences. <br /> It is unknown how the dietary source of maternal obesity longitudinally influences progeny health and the innate immune system. To this end, a maternal obesity model was generated using Drosophila. Briefly, virgin female flies were fed with a control diet (CD), a high-sugar diet (HSD), and a high-fat diet (HFD) for 7 days, and all groups mated on CD with CD-fed males. The progeny's body weight, lipidomics, genetic regulations, longevity, and locomotor outcomes were longitudinally investigated on days 0, 10, and 50. Moreover, light-induced axonal degeneration was investigated in progeny to understand whether maternal diet can impact neurodegeneration.<br /> Both HSD and HFD mothers reduced the body weight and caused the upregulation of various lipid species. While the body weight of maternal high-fat diet (HFDm) and high-sugar diet (HSDm) females stayed steady on days 0 and 10 and declined on days 50 compared to CDm, the body weight of males fluctuated between time points. The axonal degeneration was raised solely in the male progeny in the HFDm, and the bulk RNA-seq analysis revealed uniquely downregulated genes related to axonogenesis and eye development terms. Only males in the HFDm group had diminished longevity, and hemocyte-specific NF-kB knockout worsened longevity. However, challenges with bacteria did not reveal any disparity.<br /> In summary, maternal HFD and HSD result in shared and unique phenotypes in the progeny in a sex-specific manner. Further investigations should target hemocyte-specific knock-in lines, and challenge flies with different types of pathogens to reveal the exact mechanism.