Fruit flies share many sleep characteristics with humans: they sleep mostly at night, stimulants such as caffeine disrupt their rest, and poor sleep can impair memory. New research now shows they can also tell us about how sleep loss and metabolic disorders—like obesity, insulin resistance, and altered blood glucose—are linked. The study identifies a conserved gene, translin, as a key modulator that links metabolic state and sleep.
Led by researchers at Florida Atlantic University, the study published in Current Biology (April 4, 2016) demonstrates that translin acts as an essential integrator between sleep and metabolic status. These findings shed light on the neural mechanisms that cause sleep changes in response to environmental and metabolic challenges.
In humans, acute sleep deprivation increases appetite and decreases insulin sensitivity, while long-term sleep loss raises the risk of obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Equally, changes in metabolic state strongly influence sleep patterns and circadian rhythms. Yet the molecular pathways that connect sleep and metabolism are still not well understood.
“Sleep and feeding are tightly interconnected in humans, and disruptions in either process are commonly associated with metabolic disorders,” said Alex C. Keene, Ph.D., corresponding author and associate professor in the Department of Biological Sciences at FAU’s John D. MacArthur Campus. “Despite abundant evidence for links between sleep loss and metabolic dysfunction, we know little about the molecular mechanisms and how the brain integrates these signals.”
To explore these links, Keene and colleagues used Drosophila melanogaster (fruit flies) as a model. Hungry flies normally sleep less, trading rest for time spent searching for food. The researchers conducted a nervous system–specific RNA interference (RNAi) screen to identify genes required for keeping starving flies awake. They found that reducing translin expression specifically in neurons prevented the usual sleep suppression that occurs during starvation: translin-deficient flies remained as sleepy during starvation as they are when well-fed. The same inability to suppress sleep was observed in flies carrying a null mutation in translin.
During these experiments, flies were maintained on defined diets while researchers measured sleep alongside biochemical markers such as glycogen, triglycerides, and free glucose. The team was able to separate the starvation response into distinct mechanisms governing hunger and sleep suppression. Importantly, translin mutants displayed normal energy stores and normal feeding behavior, indicating that their sleep phenotype was not caused by altered nutrient storage or a blunted hunger response.
Kazuma Murakami, co–first author and a Ph.D. student in the FAU/Max Planck Florida Institute Integrative Biology and Neuroscience program, emphasized translin’s distinctive role: “Many genes influence sleep or metabolism individually, but our evidence indicates that translin uniquely integrates these processes. It is not required for general sleep modulation, nor does it change energy storage in the mutants—so the observed failure to suppress sleep during starvation is not driven by increased nutrient reserves.”
Further work localized translin’s function to a specific neuronal population. Although translin is broadly expressed in neurons, its expression in fly heads increases in response to starvation. Targeted genetic rescue and neuron-specific knockdown pointed to neurons that produce the neuropeptide Leucokinin as the critical site of translin action. Manipulating the activity of Leucokinin-producing neurons showed these cells are necessary for the normal suppression of sleep during starvation; silencing them abolished the typical starvation-induced increase in wakefulness.
These results indicate translin is not required for sensing starvation or for driving hunger-related behavior itself, but it is essential for the wakefulness response when food is absent. By identifying a gene that couples metabolic signals with sleep regulation, this study offers a clearer picture of how the brain coordinates complex behaviors like feeding and sleep and provides a foundation for understanding how metabolic disorders may interact with sleep disturbances.
Co-authors of “Translin Is Required for Metabolic Regulation of Sleep” include Maria E. Yurgel and Wesley Bollinger from the FAU/Max Planck IBAN program, along with collaborators from Scripps Florida, SUNY Binghamton, Hofstra University, Gwangju Institute of Science and Technology (South Korea), University of Bern (Switzerland), and Penn State Berks.
Source: Gisele Galoustian – Florida Atlantic University
Image Source: The image is in the public domain.
Original Research: Abstract for “translin Is Required for Metabolic Regulation of Sleep” by Kazuma Murakami, Maria E. Yurgel, Bethany A. Stahl, Pavel Masek, Aradhana Mehta, Rebecca Heidker, Wesley Bollinger, Robert M. Gingras, Young-Joon Kim, William W. Ja, Beat Suter, Justin R. DiAngelo, and Alex C. Keene in Current Biology. Published online March 24, 2016. doi:10.1016/j.cub.2016.02.013
Abstract
translin Is Required for Metabolic Regulation of Sleep
Highlights
• Flies deficient for translin fail to integrate sleep and metabolic state
• translin does not regulate stress response, overall metabolic function, or feeding
• translin functions in Leucokinin-producing neurons to regulate sleep
• Silencing Leucokinin neurons abolishes starvation-induced sleep suppression
Summary
Dysregulation of sleep or feeding carries major health consequences. In humans, acute sleep loss increases appetite and reduces insulin sensitivity, while chronic sleep deprivation is associated with heightened risk for obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Metabolic state in turn powerfully influences sleep and circadian behavior, but the molecular basis for sleep–metabolism interactions is not well defined. This study identifies translin (trsn), a conserved RNA/DNA-binding protein, as essential for starvation-induced sleep suppression. Notably, trsn mutants show normal energy stores, free glucose levels, and feeding behavior, indicating their sleep phenotype is not a result of broad metabolic dysfunction or an impaired starvation response. Although broadly expressed in neurons, trsn expression increases in fly heads during starvation. Spatially restricted genetic rescue and knockdown experiments localize trsn’s role to neurons that produce the tachykinin-family neuropeptide Leucokinin. Manipulating activity in these neurons demonstrates they are required for the wakefulness response during starvation. Together, these findings position trsn as a key integrator of sleep and metabolic state with implications for understanding how environmental perturbations disrupt sleep.
“translin Is Required for Metabolic Regulation of Sleep” by Kazuma Murakami, Maria E. Yurgel, Bethany A. Stahl, Pavel Masek, Aradhana Mehta, Rebecca Heidker, Wesley Bollinger, Robert M. Gingras, Young-Joon Kim, William W. Ja, Beat Suter, Justin R. DiAngelo, and Alex C. Keene in Current Biology. Published online March 24, 2016. doi:10.1016/j.cub.2016.02.013