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: 17.57). 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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Available from: Pankaj Kapahi, Dec 05, 2014
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    • "Feeding flies diets that are low in yeast can model protein-specific undernutrition and severely shorten lifespan (Bruce et al., 2013; Ja et al., 2009; Katewa et al., 2012; Zid et al., 2009). In this study, we asked whether microbial association could rescue the effect of protein deficiency. "
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    ABSTRACT: Microbes play an important role in the pathogenesis of nutritional disorders such as protein-specific malnutrition. However, the precise contribution of microbes to host energy balance during undernutrition is unclear. Here, we show that Issatchenkia orientalis, a fungal microbe isolated from field-caught Drosophila melanogaster, promotes amino acid harvest to rescue the lifespan of undernourished flies. Using radioisotope-labeled dietary components (amino acids, nucleotides, and sucrose) to quantify nutrient transfer from food to microbe to fly, we demonstrate that I. orientalis extracts amino acids directly from nutrient-poor diets and increases protein flux to the fly. This microbial association restores body mass, protein, glycerol, and ATP levels and phenocopies the metabolic profile of adequately fed flies. Our study uncovers amino acid harvest as a fundamental mechanism linking microbial and host metabolism, and highlights Drosophila as a platform for quantitative studies of host-microbe relationships.
    Cell Reports 02/2015; 10:1-8. DOI:10.1016/j.celrep.2015.01.018 · 8.36 Impact Factor
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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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    ABSTRACT: Phote-HrTH (Phormia terraenovae hypertrehalosemic hormone) has been demonstrated in the Diptera to be involved in flight metabolism, reproduction, and diapause. Each of these events needs the hormone’s action and requirement for carbohydrates is the common denominator. In Diptera, carbohydrates are taken up during feeding by action of the cibarial pump and are then stored in the crop. Using adult Phormia regina, both a bioassay and electrophysiological recordings show that Phote-HrTH slows down or inhibits the crop lobe muscles (P5) and, at the same time, stimulates the muscles of the pump 4 (P4) involved in pushing fluids out of the crop and up into the midgut for digestion. The EC50 for P4 was in the nanomolar range while the IC50 for P5 was 1.4-75.1 pM. The effect of Phote-HrTH on P4/5 suggests that the peptide is important in coordinating the two pumps, which are involved in moving carbohydrates up into the midgut for digestion. The adult crop organ is an essential storage organ for carbohydrates and now should be considered an important structure capable of delivering nutrients to the midgut for digestion.
    Journal of Insect Physiology 10/2014; 71. DOI:10.1016/j.jinsphys.2014.10.014 · 2.47 Impact Factor
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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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    ABSTRACT: Calorie restriction (CR), which usually refers to a 20-40% reduction in calorie intake, can effectively prolong lifespan preventing most age-associated diseases in several species. However, recent data from both human and nonhumans point to the ratio of macronutrients rather than the caloric intake as a major regulator of both lifespan and health-span. In addition, specific components of the diet have recently been identified as regulators of some age-associated intracellular signaling pathways in simple model systems. The comprehension of the mechanisms underpinning these findings is crucial since it may increase the beneficial effects of calorie restriction making it accessible to a broader population as well.
    BioMed Research International 05/2014; 2014:308690. DOI:10.1155/2014/308690 · 3.17 Impact Factor
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