Abstract
Over the past decade, numerous reports have underscored the similarities between the metabolism of Drosophila and vertebrates, with the identification of evolutionarily conserved enzymes and analogous organs that regulate carbohydrate and lipid metabolism. It is now well established that the major metabolic, energy-sensing and endocrine signaling networks of vertebrate systems are also conserved in flies. Accordingly, studies in Drosophila are beginning to unravel how perturbed energy balance impinges on lifespan and on the ensuing diseases when energy homeostasis goes awry. Here, we highlight several emerging concepts that are at the nexus between obesity, nutrient sensing, metabolic homeostasis and aging. Specifically, we summarize the endocrine mechanisms that regulate carbohydrate and lipid metabolism, and provide an overview of the neuropeptides that regulate feeding behavior. We further describe the various efforts at modeling the effects of high-fat or -sugar diets in Drosophila and the signaling mechanisms involved in integrating organ function. Finally, we draw attention to some of the cardinal discoveries made with these disease models and how these could spur new research questions in vertebrate systems.
Highlights
Metabolic syndrome – often considered a harbinger of cardiovascular disease – is a complex clinical disorder characterized primarily by abnormal blood lipid levels, central obesity, high blood pressure and elevated fasting glucose levels
Concluding remarks Here, we have highlighted some of the advances made in modeling nutrient sensing and metabolic homeostasis in Drosophila
A recent biochemical resource uncovered more than 400 different lipids that vary in expression during the life cycle of Drosophila (Guan et al, 2013), and a narrowly tuned fructose receptor was shown to function as a nutrient sensor in the brain (Miyamoto et al, 2012)
Summary
Metabolic syndrome – often considered a harbinger of cardiovascular disease – is a complex clinical disorder characterized primarily by abnormal blood lipid levels (dyslipidemia), central obesity, high blood pressure and elevated fasting glucose levels. Drosophila have organ systems that perform essentially the same metabolic functions as their vertebrate counterparts (Leopold and Perrimon, 2007). We highlight recent advances in modeling aspects of metabolic homeostasis in Drosophila, especially as it relates to diabetes, obesity and the overall aging process. Regulating metabolic homeostasis through the Drosophila orthologs of glucagon and insulin Homeostatic regulation of circulating sugar levels is essential for the health of organisms. Forced AKH expression from the fat body increases trehalose levels (trehalose is the major circulating sugar in Drosophila); in contrast, flies devoid of the AKH-producing neurons display a precipitous drop in trehalose levels (Lee and Park, 2004). Like many aspects of Drosophila metabolism, there are remarkable differences between the effects of insulin signaling
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