Pachnis, P; (2013) Growth and metabolism in adult Drosophila. Doctoral thesis , UCL (University College London).

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Abstract

In mammals, dietary nutrients regulate growth and metabolism via a network of specialised organs, including the liver and adipose tissue. Nutrient availability is coupled to growth and metabolism via Insulin and amino acid signals transduced by target of Rapamycin (TOR) and phosphatidylinositol 3-­‐kinase (PI3K). Diet also has multiple complex influences upon lipid metabolism, impacting upon fat storage and numerous other processes. It is known that TOR/PI3K signalling and lipid metabolism can be misregulated in human metabolic disorders such as type 2 diabetes but the underlying mechanisms are complex and challenging to dissect. Drosophila is emerging as a useful model for studying the integrative physiology of lipid metabolism. However, despite much research on lipid metabolism in the developing larva, relatively little is known in the adult fly about which organs other than the fat body are important. To generate new tools to study this issue, I developed an amino acid-­‐defined holidic diet and identified physiological markers of age-­‐dependent metabolism. Using these, I demonstrated that an adult cell type previously implicated in cuticular hydrocarbon synthesis, the adult oenocyte, accumulates lipid droplets in response to a dietary deficiency in methionine. This response is similar to that described for the liver and requires Lpr1, an orthologue of the mammalian Low Density Lipoprotein Receptor. Although many tissues do not grow during adulthood, oenocytes undergo a surprising amino acid and TOR/PI3K dependent volume increase without nuclear DNA replication. Cell ablations and tissue-­‐specific genetic manipulations support a model in which there is bidirectional lipid metabolic cooperation between adult oenocytes and fat body. Together, these results reveal that adult oenocytes are nutrient-­‐responsive and play a hitherto unknown role in lipid metabolism. They also indicate that there are interesting parallels between the metabolic regulation of hepatocytes and adult oenocytes.

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