Project description:Microarray-based Capture of Novel Expressed Cell type-specific Transcripts (CoNECT) to annotate tissue specific transcript isoforms in D. melanogaster
Project description:Dietary restriction (DR) is a robust environmental intervention that slows aging in various species. Changes in fat content have been associated with DR, but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown. Inhibition of acetyl CoA carboxylase (ACC), a critical enzyme in fatty acid synthesis, or fatty acid oxidation genes specifically in the muscle tissue inhibited the lifespan extension observed upon DR, suggesting a critical role for intra-myocellular fatty acid metabolism. DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. Furthermore, this increase in activity upon DR was found to partially mediate the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH) in whole flies, which increases fat metabolism, led to an increase in spontaneous activity and lifespan in a nutrient dependent manner. Together these results suggest that in Drosophila melanogaster enhanced fat metabolism in the muscle is a key metabolic adaptation in response to DR.
Project description:Dietary restriction (DR) is a robust environmental intervention that slows aging in various species. Changes in fat content have been associated with DR, but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown. Inhibition of acetyl CoA carboxylase (ACC), a critical enzyme in fatty acid synthesis, or fatty acid oxidation genes specifically in the muscle tissue inhibited the lifespan extension observed upon DR, suggesting a critical role for intra-myocellular fatty acid metabolism. DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. Furthermore, this increase in activity upon DR was found to partially mediate the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH) in whole flies, which increases fat metabolism, led to an increase in spontaneous activity and lifespan in a nutrient dependent manner. Together these results suggest that in Drosophila melanogaster enhanced fat metabolism in the muscle is a key metabolic adaptation in response to DR. 24 experimental samples were analyzed using Nimblegen oligo microarrays. Wild type samples (AL without RU486) were used as the Cy3 reference/control for all experimetal comparisons.
