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Lifelong consequences of protein deficiency during development in drosophila

Stefana, MI; (2014) Lifelong consequences of protein deficiency during development in drosophila. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Development is a vulnerable time in the life of an organism. In mammals, malnutrition during early life has profound effects on the risk of developing metabolic disease later in adulthood. Despite the well-­‐established connection between early nutrition and adult health, the underlying programming mechanisms remain unclear. This thesis develops Drosophila as a model for studying the long-­‐term physiological effects of an early low protein diet. I show that Drosophila larvae raised on food low in yeast, the major dietary source of protein, are developmentally delayed and eclose into smaller-­‐than-­‐normal adult flies (henceforth called small flies). These small flies display altered organ proportions and long-­‐term changes in metabolism. For example, I observed that lipid droplets appear specifically in the hindgut enterocytes of old control flies as a feature of normal ageing but, in small flies, they are also present in young adults. Tissue-­‐ and stage-­‐specific genetic manipulations demonstrated that these hindgut lipid droplets are regulated by the Insulin/Target of Rapamycin signalling network and require cell-­‐autonomous de novo lipogenesis. In addition, I found that a high glucose "obesogenic" adult diet interacted with low but not control [yeast] larval diets to generate flies with a two-­‐fold increase in triglycerides and ectopic lipid droplets in podocytes. The latter metabolic phenotype is recapitulated by experimentally overexpressing Brummer lipase in adipose tissue, suggesting that the underlying mechanism corresponds to lipid overflow. I also demonstrated that larval [yeast] can programme very large extensions and reductions in adult lifespan which, surprisingly, can be exchanged between co-­‐housed individuals. This suggests the existence of a social, infectious or transferable component to the mechanism of nutritional programming. Together, these findings reveal that nutritional programming is conserved from mammals to insects. They also establish a new genetic model for dissecting the mechanisms underlying the developmental origins of adult health and disease.

Type: Thesis (Doctoral)
Title: Lifelong consequences of protein deficiency during development in drosophila
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Third party copyright material has been removed from ethesis.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1446918
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