Article

Intramyocellular Fatty-Acid Metabolism Plays a Critical Role in Mediating Responses to Dietary Restriction in Drosophila melanogaster

Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Cell metabolism (Impact Factor: 16.75). 07/2012; 16(1):97-103. DOI: 10.1016/j.cmet.2012.06.005
Source: PubMed

ABSTRACT Changes in fat content have been associated with dietary restriction (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 toward increasing fatty-acid synthesis and breakdown, which is required for various responses to DR. Inhibition of fatty-acid synthesis or oxidation genes specifically in the muscle tissue inhibited life-span extension upon DR. Furthermore, DR enhances spontaneous activity of flies, which was found to be dependent on the enhanced fatty-acid metabolism. This increase in activity was found to be at least partially required for the life-span extension upon DR. Overexpression of adipokinetic hormone (dAKH), the functional ortholog of glucagon, enhances fat metabolism, spontaneous activity, and life span. Together, these results suggest that enhanced fat metabolism in the muscle and physical activity play a key role in the protective effects of DR.

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    • "Thus, it is called a hypertrehalosemic hormone (HrTH) (Wilps and Gäde, 1990). In other Diptera , such as Drosophila melanogaster (Lee and Park, 2004; Isabel et al., 2005; Bharucha et al., 2008; Kaun et al., 2008; Katewa et al., 2012) and Anopheles gambiae (Kaufmann and Brown, 2008), the influence of AKH on metabolic events or on muscle activity, spontaneous locomotion, and life span during starvation was studied. Flies are, however, also an excellent model system to investigate the putative role of AKH on crop action as postulated earlier for Hymenoptera (see above). "
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    • "Finally, inhibition of fatty acid synthesis or oxidation genes, in particular in the muscle tissue, inhibits lifespan extension upon DR [58]. "
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    • "). Also, the age-associated tendencies between our standard and DR-like regimens suggest increased synthesis (or reduced utilization) of lipids in long-living flies and agree with higher lipid stores and starvation resistance of DR flies in previous studies (Burger et al., 2007; Katewa et al., 2012). In contrast, we observed a progressive ageassociated increase in the cholesteryl esters in our long-living flies compared to controls (cluster 11). "
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