bioRxiv Science⌕ Search

bioRxiv · 10.64898/2026.10.27.762109

A conserved cold stress syndrome defines insect chill tolerance

Abstract

The ability to withstand cold is arguably one of the most important traits defining the biogeographical distribution of insects. For most species, those classified as chill susceptible, cold tolerance is limited by the ability to maintain vital physiological functions at low temperature. However, there is currently no unified understanding of how physiological failure develops during cold stress or how this process explains variation in cold sensitivity within and among species. Although disruption of ion homeostasis has been implicated in chilling injury, it remains unclear whether it represents a common physiological limit across cold stress intensities and degrees of chill tolerance. Here, we tested whether ion balance disruption represents a unifying physiological syndrome of chill susceptibility by simultaneously quantifying cold mortality and hemolymph [K] in Drosophila. We examined this relationship across i) a broad range of cold stress intensities, ii) 25 species spanning extensive variation in cold sensitivity, biogeography and phylogeny, and iii) acclimation groups of D. melanogaster developed between 12 and 27{degrees}C. Across all comparisons, mortality was associated with the same cold-stress response, characterized by progressive hyperkalemia and mortality following a ~150% increase in hemolymph [K] above baseline ([K]crit). In contrast, adaptive and plastic variation in cold sensitivity was explained by differences in the critical temperature at which ion homeostasis failed (Tc). Extending this framework to published data from other insect orders revealed a remarkably similar [K]crit, suggesting that ionoregulatory collapse represents a conserved physiological constraint defining insect cold survival.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Andersen, M. K., Jakobsen, S. F., Nielsen, E. S., Siddika, A., Byrge, C. G., Overgaard, J.. 2026-11-01. A conserved cold stress syndrome defines insect chill tolerance. https://doi.org/10.64898/2026.10.27.762109

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Development of a mouse model to investigate the effect of exertional heat stress on skeletal muscle

Increased body temperature during exercise is considered a risk factor for skeletal muscle injury. There are various murine models of heat exposure-induced organ injury. The present study has attempted to develop a mouse model of skeletal muscle injury associated with exercise-induced whole body hyperthermia. C57BL/6J male mice were randomly assigned into control (CON) and exercise (EX) groups (n = 6 per group). EX group exercised on a programmed, motorized wheel, while CON group remained in a mouse cage in an environmental chamber at 35 degree C for ~3 hours. EX group showed a significantly higher average body core temperature (38.5 degree C +/- 0.3) compared to CON group (37.3 degree C +/- 0.3). Plasma myoglobin levels were significantly higher in EX group than in CON. Additionally, exercise significantly impaired skeletal muscle and mitochondria, as evidenced by elevated TBARS and caspase-3 levels and reduced ATP and Complex IV levels in gastrocnemius muscles in EX group. We developed a mouse model of exercise-induced mild whole body hyperthermia that recapitulates many key features of heat stress-induced skeletal muscle injury. This novel model will provide a useful tool for future investigation into the mechanisms of and intervention strategies for muscle exertional heat injury.

physiology↗

Burn Wound Excision Drives Acute Hypermetabolism in Mice with Scald Burns

Hypermetabolism (elevated resting energy expenditure) is a hallmark of the pathophysiological response to burns. The contribution of wound excision to acute burn-induced hypermetabolism remains unclear. Importantly, while burn wound excision is a standard component of clinical burn care, it is not typically included in rodent models of burn injury. Here, we tested the hypothesis that burn wound excision drives the acute hypermetabolic response to burn trauma. C57BL/6J mice (n=12-18 per group; ~6-weeks old; 50% male) were acclimated to thermoneutral housing (30C) for 6-weeks. All mice underwent baseline body composition scans and metabolic phenotyping to determine total (TEE) and resting energy expenditure (REE). Mice were then randomized to either sham (control), scald burn (burn), wound excision (excision), or scald burn followed by immediate wound excision (burn+excision) groups. Burns and wound excisions involved ~15% of the body surface area. Mice then recovered for 14 days while individually housed in metabolic phenotyping cages. At day 14 post-injury, mice underwent a second body composition scan prior to euthanasia. There were no fatalities in the control or burn groups, whereas 23% (n=7) and 34% (n=11) of mice in the excision and burn+excision groups died or were euthanized during the 14-day recovery period. Male and female mice exhibited broadly similar responses to injury in terms of REE and TEE. Compared to control, REE was greater in burn (47%), excision (102%), and burn+excision groups (136%) during the first week post-injury (P<0.001 for all). Compared to control mice, wound excision (alone or following burns) resulted in a greater acute loss in body mass than burn injury alone. However, this cachectic response was more sustained in male mice compared to females. Similarly, wound excision (alone or following burns) resulted in greater bone mineral content and density loss compared to sham and burn alone in both sexes. Wound excision is a key contributor to the hypermetabolic and cachectic response to burn trauma in mice. We posit that rodent studies aiming to recapitulate burn-induced hypermetabolism and cachexia should include burn wound excision to better model the clinical sequelae to burns.

physiology↗

Reduced cerebral blood flow and metabolic rate trigger an adaptive mitochondrial remodeling program in a Down syndrome mouse model

Mitochondrial dysfunction is a central feature of Down syndrome (DS), yet how trisomy 21 affects brain bioenergetics across scales--from gene transcription to cellular function to whole-brain metabolism--remains poorly understood. Here, we use the Dp16(1)Yey/+ (abbreviated Dp16) DS mouse model, which carries ~115 triplicated gene orthologs of human chromosome 21, to address this major knowledge gap and to provide direct in vivo evidence of brain-wide metabolic deficit in DS. Using magnetic resonance imaging (MRI) approaches, we show that Dp16 mice have reduced cerebral blood flow and metabolic rate of oxygen, with effects more pronounced in males than in females. Despite the suppression of cerebral metabolic rate, mitochondrial respiratory capacity and ATP synthase activity are largely preserved across brain regions, with sex differences noted. Transcriptomic analyses reveal marked upregulation of mitochondrial OXPHOS genes and the convergence of biological pathways related to proteostasis and mitochondrial function across brain regions, with male cortex and female cerebellum showing the biggest change. Collectively, our data suggest that a brain-wide metabolic deficit in Dp16 mice triggers an adaptive mitochondrial remodeling program across the brain to support bioenergetic demands. This compensatory response, however, is insufficient to normalize the metabolic dysfunction in Dp16 mice. Our findings underscore the value of integrating functional assessments at the organismal and tissue levels with transcriptomic changes to gain a systems view of physiologic perturbations and adaptations in the DS brain which may influence phenotypic outcomes.

physiology↗