Insulin signalling elicits hunger-induced feeding in Drosophila (original) (raw)
Related papers
Insulin signalling activates multiple feedback loops to elicit hunger-induced feeding in Drosophila
Insulin, a highly conserved peptide hormone, links nutrient availability to metabolism and growth in animals. Besides this, in fed states insulin levels are high and insulin acts as a satiety hormone. In animals that are food deprived insulin levels remain low which facilitates hunger induced feeding. Contrary to expectations, we present evidence for persistent Drosophila insulin-like peptide gene expression and insulin signalling during initial phases of starvation. Maintenance of insulin signalling is crucial to sustain feeding responses during initial stages of starvation. Insulin signalling acts in a feedback loop involving the abdominal fatbody to maintain dilp gene expression in the early stages of food deprivation. Furthermore, another feedback regulatory loop between insulin-producing cells (IPCs) and neurons that produce the orectic hormone short-neuropeptide-F (sNPF), maintains sNPF levels and triggers feeding behavior. Thus, insulin acts through multiple feedback regulato...
Journal of Biological Chemistry, 2011
Background: Little is known about the molecular mechanisms underlying animal feeding behavior. Result: We identified a new gene, Anorexia (Anox), which encodes an acyl-CoA binding protein with an ankyrin repeat domain. Conclusion: Anox has an essential role in controlling feeding activities in Drosophila by regulating insulin signaling. Significance: Identification of Anox can develop a better knowledge of mechanisms underlying animal feeding behavior. Feeding activities of animals, including insects, are influenced by various signals from the external environment, internal energy status, and physiological conditions. Full understanding of how such signals are integrated to regulate feeding activities has, however, been hampered by a lack of knowledge about the genes involved. Here, we identified an anorexic Drosophila melanogaster mutant (GS1189) in which the expression of a newly identified gene, Anorexia (Anox), is mutated. In Drosophila larvae, Anox encodes an acyl-CoA binding protein with an ankyrin repeat domain that is expressed in the cephalic chemosensory organs and various neurons in the central nervous system (CNS). Loss of its expression or disturbance of neural transmission in Anox-expressing cells decreased feeding activity. Conversely, overexpression of Anox in the CNS increased food intake. We further found that Anox regulates expression of the insulin receptor gene (dInR); overexpression and knockdown of Anox in the CNS, respectively, elevated and repressed dInR expression, which altered larval feeding activity in parallel with Anox expression levels. Anox mutant adults also showed significant repression of sugar-induced nerve responses and feeding potencies. Although Anox expression levels did not depend on the fasting and feeding states cycle, stressors such as high temperature and desiccation significantly repressed its expression levels. These results strongly suggest that Anox is essential for gustatory sensation and food intake of Drosophila through regulation of the insulin signaling activity that is directly regulated by internal nutrition status. Therefore, the mutant strain lacking Anox expression cannot enhance feeding potencies even under starvation.
Molecular mechanisms of metabolic regulation by insulin in Drosophila
Biochemical Journal, 2010
The insulin signalling pathway is highly conserved from mammals to Drosophila. Insulin signalling in the fly, as in mammals, regulates a number of physiological functions, including carbohydrate and lipid metabolism, tissue growth and longevity. In the present review, I discuss the molecular mechanisms by which insulin signalling regulates metabolism in Drosophila, comparing and contrasting with the mammalian system. I discuss both the intracellular signalling network, as well as the communication between organs in the fly.
Feeding regulation in Drosophila
Current opinion in neurobiology, 2014
Neuromodulators play a key role in adjusting animal behavior based on environmental cues and internal needs. Here, we review the regulation of Drosophila feeding behavior to illustrate how neuromodulators achieve behavioral plasticity. Recent studies have made rapid progress in determining molecular and cellular mechanisms that translate the metabolic needs of the fly into changes in neuroendocrine and neuromodulatory states. These neuromodulators in turn promote or inhibit discrete feeding behavioral subprograms. This review highlights the links between physiological needs, neuromodulatory states, and feeding decisions.
The Temporal Requirements for Insulin Signaling During Development in Drosophila
PLoS Biology, 2005
Recent studies have indicated that the insulin-signaling pathway controls body and organ size in Drosophila, and most metazoans, by signaling nutritional conditions to the growing organs. The temporal requirements for insulin signaling during development are, however, unknown. Using a temperature-sensitive insulin receptor (Inr) mutation in Drosophila, we show that the developmental requirements for Inr activity are organ specific and vary in time. Early in development, before larvae reach the ''critical size'' (the size at which they commit to metamorphosis and can complete development without further feeding), Inr activity influences total development time but not final body and organ size. After critical size, Inr activity no longer affects total development time but does influence final body and organ size. Final body size is affected by Inr activity from critical size until pupariation, whereas final organ size is sensitive to Inr activity from critical size until early pupal development. In addition, different organs show different sensitivities to changes in Inr activity for different periods of development, implicating the insulin pathway in the control of organ allometry. The reduction in Inr activity is accompanied by a two-fold increase in free-sugar levels, similar to the effect of reduced insulin signaling in mammals. Finally, we find that varying the magnitude of Inr activity has different effects on cell size and cell number in the fly wing, providing a potential linkage between the mode of action of insulin signaling and the distinct downstream controls of cell size and number. We present a model that incorporates the effects of the insulin-signaling pathway into the Drosophila life cycle. We hypothesize that the insulinsignaling pathway controls such diverse effects as total developmental time, total body size and organ size through its effects on the rate of cell growth, and proliferation in different organs. Citation: Shingleton AW, Das J, Vinicius L, Stern DL, (2005) The temporal requirements for insulin signaling during development in Drosophila. PLoS Biol 3(9): e289.
Factors that regulate insulin producing cells and their output in Drosophila
Insulin-like peptides (ILPs) and growth factors (IGFs) not only regulate development, growth, reproduction, metabolism, stress resistance, and lifespan, but also certain behaviors and cognitive functions. ILPs, IGFs, their tyrosine kinase receptors and downstream signaling components have been largely conserved over animal evolution. Eight ILPs have been identified in Drosophila (DILP1-8) and they display cell and stage-specific expression patterns. Only one insulin receptor, dInR, is known in Drosophila and most other invertebrates. Nevertheless, the different DILPs are independently regulated transcriptionally and appear to have distinct functions, although some functional redundancy has been revealed. This review summarizes what is known about regulation of production and release of DILPs in Drosophila with focus on insulin signaling in the daily life of the fly. Under what conditions are DILP-producing cells (IPCs) activated and which factors have been identified in control of IPC activity in larvae and adult flies? The brain IPCs that produce DILP2, 3 and 5 are indirectly targeted by DILP6 and a leptin-like factor from the fat body, as well as directly by a few neurotransmitters and neuropeptides. Serotonin, octopamine, GABA, short neuropeptide F (sNPF), corazonin and tachykinin-related peptide have been identified in Drosophila as regulators of IPCs. The GABAergic cells that inhibit IPCs and DILP release are in turn targeted by a leptin-like peptide (unpaired 2) from the fat body, and the IPC-stimulating corazonin/sNPF neurons may be targeted by gut-derived peptides. We also discuss physiological conditions under which IPC activity may be regulated, including nutritional states, stress and diapause induction.
Control of Metabolism and Growth Through Insulin-Like Peptides in Drosophila
Diabetes, 2006
Insulin signaling is a conserved feature in all metazoans. It evolved with the appearance of multicellularity, allowing primordial metazoans to respond to a greater diversity of environmental signals. The insulin signaling pathway is highly conserved in insects and particularly in Drosophila, where it has been extensively studied in recent years and shown to control metabolism, growth, reproduction, and longevity. Because misregulation of the insulin/IGF pathway in humans plays a role in many medical disorders, such as diabetes and various types of cancer, unraveling the regulation of insulin/IGF signaling using the power of a genetically tractable organism like Drosophila may contribute to the amelioration of these major human pathologies.
Circadian clock regulates various behavioral, metabolic and physiological processes to occur at the most suitable time of the day. The most apparent behavioral outputs of the clock are activity-rest rhythm and feeding. While clock regulates these two behaviors through interconnected neuronal circuits, the precise pathway through which the clock coordinates metabolism in accordance with the behavioral rhythms largely remains to be elucidated. This study was aimed to elucidate the role of two circadian relevant metabolic neuropeptides, short neuropeptide F (sNPF) and Drosophila Insulin Like Peptide 2 (DILP2) in triglyceride metabolism, starvation-mediated hyperactivity, and food intake in Drosophila. The results showed that snpf transcripts exhibit significant rhythmicity under 12:12 hour light-dark cycles (LD) and constant darkness (DD). Knockdown of sNPF in sNPF producing neurons enhanced the starvation-mediated hyperactivity in flies compared to the control. Further studies showed ...