Innate immunity is the primary and most ancient defense against infection. Although critical to survival, coordinating protection against a foreign organism is energetically costly, creating the need to reallocate substrates from nonessential functions, such as growth and nutrient storage. However, the mechanism by which infection or inflammation leads to a reduction in energy utilization by these dispensable processes is not well understood. Here, we demonstrate that activation of the Toll signaling pathway selectively in the fat body, the major immune and lipid storage organ of the fruit fly, Drosophila melanogaster, leads to both induction of immunity and reallocation of resources. Toll signaling in the fat body suppresses insulin signaling both within these cells and non-autonomously throughout the organism, leading to a decrease in both nutrient stores and growth. These data suggest that communication between these two regulatory systems evolved as a means to divert energy in times of need from organismal growth to the acute requirement of combating infection.fat body ͉ immunity ͉ Toll ͉ insulin

Circadian rhythms are regulated by a synchronized system of central and peripheral clocks. Here we show that a clock in the Drosophila fat body drives rhythmic expression of genes involved in metabolism, detoxification, the immune response and steroid hormone regulation. Some of these genes cycle even when the fat body clock is disrupted indicating they are regulated by exogenous factors. Food is an important stimulus as limiting food availability to a six-hour interval each day drives rhythmic expression of genes in the fat body. Restricting food to a time of day when consumption is typically low desynchronizes internal rhythms because it alters the phase of rhythmic gene expression in the fat body without affecting the brain clock. Flies maintained on this paradigm produce fewer eggs than those restricted to food at the normal time. These data suggest that desynchrony of endogenous rhythms, caused by aberrant feeding patterns, affects reproductive fitness.

While course-based research in genomics can generate both knowledge gains and a greater appreciation for how science is done, a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. Nonetheless, this is a very cost-effective way to reach larger numbers of students.

A phylogenetically conserved response to nutritional abundance is an increase in insulin signaling, which initiates a set of biological responses dependent on the species. Consequences of augmented insulin signaling include developmental progression, cell and organ growth, and the storage of carbohydrates and lipids. Here, we address the evolutionary origins of insulin's positive effects on anabolic lipid metabolism by selectively modulating insulin signaling in the fat body of the fruit fly, Drosophila melanogaster. Analogous to the actions of insulin in higher vertebrates, those in Drosophila include expansion of the insect fat cell mass both by increasing the adipocyte number and by promoting lipid accumulation. The ability of insulin to accomplish the former depends on its capacity to bring about phosphorylation and inhibition of the transcription factor Drosophila FOXO (dFOXO) and the serine/threonine protein kinase shaggy, the fly ortholog of glycogen synthase kinase 3 (GSK3). Increasing the amount of triglyceride per cell also depends on the phosphorylation of shaggy but is independent of dFOXO. Thus, the findings of this study provide evidence that the control of fat mass by insulin is a conserved process and place dFOXO and shaggy/GSK3 downstream of the insulin receptor in controlling adipocyte cell number and triglyceride storage, respectively.The recent epidemic of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM) has renewed interest in fundamental principles of metabolic homeostasis. Much attention has been directed to the appropriate control of carbohydrate metabolism, as elevated glucose is the cardinal, defining sign of diabetes mellitus. Nonetheless, an integrated and finely tuned balance of lipid storage and breakdown is also essential for metabolic well-being. Defects in lipid metabolism not only contribute directly to a number of diseases, such as the inherited lipodystrophies, the metabolic syndrome, and atherosclerosis, but also are an integral component of T2DM. In fact, it has been argued persuasively that T2DM is regarded as a disorder of glucose metabolism for purely historical reasons and that lipid abnormalities are as or more important to the pathogenesis and consequences of the disease (33). Thus, a refined, mechanistic understanding of the normal control of lipid storage and mobilization is critical.The major regulators of lipid synthesis and breakdown are glucose and the peptide hormone insulin. It is now clear that insulin signals through a canonical pathway that is phylogenetically conserved, controlling growth, development, and ageing in invertebrates (Caenorhabditis elegans and Drosophila melanogaster) and metabolic outputs in vertebrates (rodents and humans) (17, 37). For example, in mammals, insulin regulates hepatic, muscle, and adipocyte glucose metabolism in a manner dependent on signaling through phosphatidylinositol 3-kinase (PI3K) and its downstream intermediary, Akt, also known as protein kinase B (12, 44). This same pathway has also been implicated in ...