ROS and hypoxia signaling regulate periodic metabolic arousal during insect dormancy to coordinate glucose, amino acid, and lipid metabolism

Metabolic suppression is a hallmark of animal dormancy that promotes overall energy savings. Some diapausing insects and some mammalian hibernators have regular cyclic patterns of substantial metabolic depression alternating with periodic arousal where metabolic rates increase dramatically. Previous studies, largely in mammalian hibernators, have shown that periodic arousal is driven by an increase in aerobic mitochondrial metabolism and that many molecules related to energy metabolism fluctuate predictably across periodic arousal cycles. However, it is still not clear how these rapid metabolic shifts are regulated. We first found that diapausing flesh fly pupae primarily use anaerobic glycolysis during metabolic depression but engage in aerobic respiration through the tricarboxylic acid cycle during periodic arousal. Diapausing pupae also clear anaerobic by-products and regenerate many metabolic intermediates depleted in metabolic depression during arousal, consistent with patterns in mammalian hibernators. We found that decreased levels of reactive oxygen species (ROS) induced metabolic arousal and elevated ROS extended the duration of metabolic depression. Our data suggest ROS regulates the timing of metabolic arousal by changing the activity of two critical metabolic enzymes, pyruvate dehydrogenase and carnitine palmitoyltransferase I by modulating the levels of hypoxia inducible transcription factor (HIF) and phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK). Our study shows that ROS signaling regulates periodic arousal in our insect diapasue system, suggesting the possible importance ROS for regulating other types of of metabolic cycles in dormancy as well.

miR-31-5p regulates cold acclimation of the wood-boring beetle Monochamus alternatus via ascaroside signaling

Background Survival to cold stress in insects living in temperate environments requires the deployment of strategies that lead to physiological changes involved in freeze tolerance or freeze avoidance. These strategies may consist of, for instance, the induction of metabolic depression, accumulation of cryoprotectants, or the production of antifreeze proteins, however, little is known about the way such mechanisms are regulated and the signals involved in their activation. Ascarosides are signaling molecules usually known to regulate nematode behavior and development, whose expression was recently found to relate to thermal plasticity in the Japanese pine sawyer beetle Monochamus alternatus. Accumulating evidence also points to miRNAs as another class of regulators differentially expressed in response to cold stress, which are predicted to target genes involved in cold adaptation of insects. Here, we demonstrate a novel pathway involved in insect cold acclimation, through miRNA-mediated regulation of ascaroside function. Results We initially discovered that experimental cold acclimation can enhance the beetle’s cold hardiness. Through screening and functional verification, we found miR-31-5p, upregulated under cold stress, significantly contributes to this enhancement. Mechanistically, miR-31-5p promotes production of an ascaroside (asc-C9) in the beetle by negatively targeting the rate-limiting enzyme, acyl-CoA oxidase in peroxisomal β-oxidation cycles. Feeding experiments with synthetic asc-C9 suggests it may serve as a signal to promote cold acclimation through metabolic depression and accumulation of cryoprotectants with specific gene expression patterns. Conclusions Our results point to important roles of miRNA-mediated regulation of ascaroside function in insect cold adaptation. This enhanced cold tolerance may allow higher survival of M. alternatus in winter and be pivotal in shaping its wide distribution range, greatly expanding the threat of pine wilt disease, and thus can also inspire the development of ascaroside-based pest management strategies.

Flight activity and glycogen depletion on a low-carbohydrate diet

ABSTRACTGlycogen is a critical store for locomotion. Depleted glycogen stores are associated with increased fatigue during exercise. The reduced effectiveness of low-carbohydrate diets for weight loss over longer time periods may arise because such diets reduce glycogen stores and thereby energy expenditure via physical activity. To explore the effect of a low-carbohydrate diet on activity and glycogen utilisation, we fed adult Drosophila melanogaster a standard or low-carbohydrate diet for 9 days and measured patterns of flight activity and rates of glycogen depletion. We hypothesised that flight activity and rates of glycogen depletion would be reduced on a low-carbohydrate diet. Flight activity was elevated in the low-carbohydrate group but glycogen depletion rates were unchanged. We conclude that increased activity is probably a foraging response to carbohydrate deficiency and speculate that the previously demonstrated metabolic depression that occurs on a low-carbohydrate diet in this species may allow for increased flight activity without increased glycogen depletion.

Shallow metabolic depression and human spaceflight: a feasible first step

Synthetic torpor is an induced state of deep metabolic depression (MD) in an organism that does not naturally employ regulated and reversible MD. If applied to spaceflight crewmembers, this metabolic state may theoretically mitigate numerous biological and logistical challenges of human spaceflight. These benefits have been the focus of numerous recent articles where, invariably, they are discussed in the context of hypothetical deep MD states in which the metabolism of crewmembers is profoundly depressed relative to basal rates. However, inducing these deep MD states in humans, particularly humans aboard spacecraft, is currently impossible. Here, we discuss shallow MD as a feasible first step toward synthetic torpor during spaceflight and summarize perspectives following a recent NASA-hosted workshop. We discuss methods to safely induce shallow MD (e.g., sleep and slow wave enhancement via acoustic and photoperiod stimulation; moderate sedation via dexmedetomidine), which we define as an ~20% depression of metabolic rate relative to basal levels. We also discuss different modes of shallow MD application (e.g., habitual versus targeted, whereby shallow MD is induced routinely throughout a mission or only under certain circumstances, respectively) and different spaceflight scenarios that would benefit from its use. Finally, we propose a multistep development plan toward the application of synthetic torpor to human spaceflight, highlighting shallow MD’s role. As space agencies develop missions to send humans further into space than ever before, shallow MD has the potential to confer health benefits for crewmembers, reduce demands on spacecraft capacities, and serve as a testbed for deeper MD technologies.