Cold Exposure Research Articles

Accelerated Frostbite-Induced Acroosteolysis in Pediatric Insensate Hand: A Case Report and Literature Review.

In pediatric patients, frostbite is a well-documented cause of epiphyseal cartilage destruction and subsequent growth deformity of the affected phalanges. Cases of full acroosteolysis, also referred to as phalangeal osteolysis, of distal phalanges as soon as three months after cold exposure have yet to be reported. We describe a complicated case of frostbite-associated phalangeal osteolysis in the dominant hand of a nine-year-old patient, in the context of post-traumatic insensate hand after sustaining prior electrical burn injuries. This case demonstrates the unique sequela of pediatric frostbite injury involving early loss of the distal phalanx through resorption of the bone and parallel soft tissue retraction, rendering early plastic surgery reconstruction impractical. Reconstructive strategies for frostbite injury in pediatric patients will need to account for the individualized dynamic tissue changes that develop in the months after cold exposure.

The impact of residential winter HVAC usage behavior on arthritis in older adults: A PLS-SEM analysis

Environmental factors like temperature and humidity have been shown to influence arthritis symptoms in older adults, and HVAC equipment can regulate indoor environmental parameters. This study aimed to explore the pathways and effectiveness of residential HVAC usage behavior during winter on arthritis conditions. Conducted across four major climate zones in China, this cross-sectional study involved 3579 older adults aged 60–74 years and collected data on demographics, residential environments, lifestyles, and health outcomes. Utilizing Partial Least Squares - Structural Equation Modeling (PLS-SEM), a complex structural equation model (SEM) and an HVAC-Health mediation model was developed to analyze the relationships among influencing factors and health outcomes. Results revealed that socio-economic status, building characteristics, lifestyles, HVAC usage behavior, and indoor environmental exposure significantly affect the frequency of arthritis flare-ups (p < 0.05). Specifically, lifestyles, indoor wet and cold exposures have strong direct effects on health outcomes, with path coefficients of 0.178, 0.155 and 0.143, respectively. Moreover, HVAC usage indirectly influences health through mediators, with cold exposure (β = 0.045, p < 0.001), air pollution (β = 0.025, p < 0.001), and wet exposure (β = 0.012, p = 0.001) ranked in terms of their mediating effects. This research underscores the crucial role of HVAC systems in mitigating arthritis symptoms in older adults, advocating for enhanced implementation of HVAC technologies in senior housing to promote health and well-being. The originality of this study lies in employing the PLS-SEM method to elucidate how the indoor environment—particularly under the premise of HVAC usage—affect arthritis symptoms in older adults.

Cardiac electrical and functional activity following an outdoor cold-water swimming event

AimsParticipation in outdoor cold-water swimming (OCWS) events combines endurance exercise and cold exposure. Concerns have emerged about the potential risk of acute adverse cardiac events during OCWS, particularly during endurance events. We analysed the effect of prolonged OCWS on cardiac function in trained athletes. MethodsThe swimming event consisted of laps over a 1000-m course, for up to 6 h, in water at 15 °C. Twenty participants (11 males, 47.3 ± 8.6 years old) were included. Core temperature (Tcore) was monitored using an ingestible temperature sensor during and up to 1 h after the swim. Body composition, blood pressure, electrocardiogram (ECG), and transthoracic echocardiography were assessed 1 day before the event and within the first hour upon completion of the swim. ResultsMean body mass index was 27.1 ± 5.1 kg/m2 and fat mass was 25.2 ± 9.1 %. Mean duration of swimming was 214 ± 115 min. Minimum Tcore was 35.6 ± 1.3 °C. A significant lengthening of the QT interval corrected (QTc) for heart rate was observed post-exercise (437.7 ± 27.7 vs. 457.2 ± 35.9 ms, p = 0.012), with 5 participants exhibiting post-exercise QTc >500ms. OCWS did not alter the biventricular systolic function and left ventricular relaxation. No correlation was observed between ΔQTc and ΔTcore. ConclusionOCWS seemed to acutely delay post-exercise cardiac repolarization without alteration of cardiac function in a healthy trained population. Additional investigations would be warranted to explore the clinical implications of QT lengthening and its relationship with autonomic nervous system regulation during OCWS.

Cardiovascular morbidity risk attributable to thermal stress: analysis of emergency ambulance dispatch data from Shenzhen, China

BackgroundClimate change has raised scientific interest in examining the associations of weather conditions with adverse health effects, while most studies determined human thermal stress using ambient air temperature rather than the thermophysiological index.ObjectivesTo evaluate the association between emergency ambulance dispatches (EADs) related to cardiovascular causes and heat/cold stress in Shenzhen, a city in southern China, with the aim of providing new insights for local policymakers.MethodsA time series analysis using ambulance dispatch data of cardiovascular diseases in Shenzhen, China (2013–2019) was conducted. A quasi-Poisson nonlinear distributed lag model was applied to explore the relationship between emergency ambulance dispatches (EADs) due to cardiovascular causes and thermal stress (determined by Universal Thermal Climate Index, UTCI). Attributable fractions were estimated to identify which UTCI ranges have a greater health impact.ResultsThe relationship between UTCI and EADs due to cardiovascular diseases exhibits a reverse J-shaped curve. The effects of cold stress were immediate and long-lasting, whereas the effects of heat stress were non-significant. Compared with the optimal equivalent temperature (71st percentile of UTCI, 29.22 °C), the relative risks for cumulative (0–21 days) exposures to cold stress (1st percentile, − 0.13 °C; 5th percentile, 7.68 °C) were 1.55 (95%CI:1.28,1.88) and 1.44 (95%CI:1.22,1.69), respectively. Thermal (cold and heat) stress was responsible for 10.81% (95%eCI: 5.67%,15.43%) of EADs for cardiovascular diseases, with 9.46% (95%eCI: 3.98%,14.40%) attributed to moderate cold stress (2.5th ~ 71st percentile). Greater susceptibility to cold stress was observed for males and the elderly. Heat stress showed harmful effects in the warm season.ConclusionsOur results demonstrated that cold exposure elevates the risk of EADs for cardiovascular causes in Shenzhen, and moderate cold stress cause the highest burden of ambulance dispatches. Health authorities should consider effective adaptation strategies and interventions responding to cold stress to reduce the morbidity of cardiovascular diseases.

Sex differences in autonomic functions and cognitive performance during cold-air exposure and cold-water partial immersion.

This study investigated the differences between males and females in autonomic functions and cognitive performance during cold-air exposure and cold-water partial-immersion compared to a room temperature-air environment. Although several studies have investigated the effects of cold-air or cold-water exposures on autonomic function and cognitive performance, biological sex differences are often under-researched. Twenty-two males and nineteen females participated in the current study. Subjects completed a battery of cognitive tasks based upon those used within the Defense Automated Neurobehavioral Assessment (DANA), consisting of five subtasks that assess simple and procedural reaction time, spatial manipulation, attention, and immediate memory. In total, subjects took the battery within a 15-minute period across 30-minute intervals throughout the duration of environmental exposure. Across three separate days, subjects were exposed to three different environmental conditions: room temperature air (23°C), cold air (10°C), and cold water (15°C; in which subjects were immersed up to their necks). Room temperature and cold-air conditions consisted of five sessions (about 2.5h), and the cold-water condition consisted of three sessions (about 1.5h). During each experimental condition, physiological data were collected to assess autonomic function, including electrodermal activity (EDA) data and heart rate variability (HRV) derived from electrocardiogram signals. Females showed slower reaction time in spatial manipulation tasks, immediate memory, and attention during cold-air exposures compared to room temperature air, whereas the performance of males were similar or better during cold-air exposures compared to room temperature air. Cold-water immersion affected the immediate memory performance of males. Both males and females exhibited smaller EDA amplitudes during cold-air and cold-water conditions compared to room temperature air. For HRV, only male subjects exhibited significantly greater values in low-frequency and very-low-frequency components during cold air exposure compared to the normal condition. Sex introduces important differences in cognitive performance and autonomic functions during exposure to cold-air and cold-water. Therefore, sex should be considered when assessing the autonomic nervous system in cold environments and when establishing optimal thermal clothing for performance in operational environments. Our findings can assist with determination of operational clothing, temperature in operating environment, and personnel deployment to operational sites, particularly in settings involving both males and females.

Chronic cold exposure reprograms feeding-regulated LPL activity in white adipose tissues through hepatic ANGPTL3 and ANGPTL8

Chronic cold exposure reprograms feeding-regulated LPL activity in white adipose tissues through hepatic ANGPTL3 and ANGPTL8

SOX4 facilitates brown fat development and maintenance through EBF2-mediated thermogenic gene program in mice.

Brown adipose tissue (BAT) is critical for non-shivering thermogenesis making it a promising therapeutic strategy to combat obesity and metabolic disease. However, the regulatory mechanisms underlying brown fat formation remain incompletely understood. Here, we found SOX4 is required for BAT development and thermogenic program. Depletion of SOX4 in BAT progenitors (Sox4-MKO) or brown adipocytes (Sox4-BKO) resulted in whitened BAT and hypothermia upon acute cold exposure. The reduced thermogenic capacity of Sox4-MKO mice increases their susceptibility to diet-induced obesity. Conversely, overexpression of SOX4 in BAT enhances thermogenesis counteracting diet-induced obesity. Mechanistically, SOX4 activates the transcription of EBF2, which determines brown fat fate. Moreover, phosphorylation of SOX4 at S235 by PKA facilitates its nuclear translocation and EBF2 transcription. Further, SOX4 cooperates with EBF2 to activate transcriptional programs governing thermogenic gene expression. These results demonstrate that SOX4 serves as an upstream regulator of EBF2, providing valuable insights into BAT development and thermogenic function maintenance.

Cold Exposure Therapy Sensitizes Nanodrug-Mediated Radioimmunotherapy of Breast Cancer.

Cold exposure (CE) therapy can quickly induce tumor starvation by brown adipose tissue (BAT) thermogenesis. Exploring the combined antitumor mechanism of CE and traditional therapies (such as radiotherapy (RT)) is exciting and promising. In this study, we investigated the effect of CE in combination with nitric oxide (NO) gas therapy on sensitizing tumors to RT and promoting tumor radio-immunotherapy. We first constructed a liposome (SL) loaded with the NO prodrug S-nitroso-N-acetylpenicillamine (SNAP). When SL is injected, the glutathione (GSH) within the tumor region promotes the release of NO from SNAP. Subsequently, the superoxide anion produced by RT reacts with NO to generate peroxynitrite (ONOO-), which has strong oxidative properties and induces cell death. Meanwhile, the mice were exposed to a CE environment of 4 °C. CE-mediated BAT thermogenesis induced tumor starvation, which led to a decrease in ATP and GSH content within the tumor as well as an improvement in the hypoxic microenvironment and a decrease in myeloid-derived suppressor cells. All of the above have promoted the effectiveness of RT and activated the systemic antitumor immunity. In the bilateral tumor experiment, treatment of the primary tumor inhibited the growth of the distant tumor and promoted the infiltration of CD8+ T cells into the tumor. These findings reveal that the synergy of CE, NO gas therapy, and RT could confer high effective anticancer effects, providing possibilities in personalized cancer treatment.

Influence of climate change on flowering phenology of Yoshino cherry at its southern distribution limit.

To clarify the influence of climate change on the flowering phenology of Yoshino cherry at its southern distribution limit, we examined the relationship between cold exposure for endodormancy release (chilling requirement) and heat requirement for bud growth on Hachijojima Island, Japan, from 1948 to 2024. Cold exposure and heat requirement had a significant relationship approximated by linear or log-linear functions. In years with less cold exposure, the first flowering dates were much later than normal, in accordance with the higher heat requirement. Our results indicate that the variation in the balance between cold exposure and heat requirement depending on the pattern of annual air temperature change is likely to vary the first flowering date greatly at the distribution limit of Yoshino cherry.

FDG Uptake in Brown Adipose Tissue Activated by a Long-Acting β2-Adrenergic Receptor Agonist Inhaler Prescribed for Bronchial Asthma.

We herein report a case of an elderly woman in whom brown adipose tissue (BAT) was visible on 18 F-FDG PET imaging performed in the summer. In this patient, none of the well-known factors that induce BAT activation in adults, including cold exposure, catecholamine-producing tumors, or β3-adrenergic receptor agonists administration, were present. Daily inhalation of a long-acting β2-adrenergic agonist for treatment of her bronchial asthma was considered the cause of her BAT visualization. This case suggests the need to consider β2-adrenergic receptor agonists as a cause of BAT visualization.

7951 The Response of HPT Axis &amp; BAT to Cold Exposure Is Delayed in Female Rats Compared to Males

Abstract Disclosure: A. Gutiérrez-Mata: None. L. Jaimes-Hoy: None. I. Sotelo-Rivera: None. F. Romero-Arteaga: None. R.M. Uribe: None. J.L. Charli: None. P. Joseph-Bravo: None. Cold exposure activates the sympathetic nervous system releasing NE in thermogenic brown adipose tissue (BAT) and in parallel, the Hypothalamus-Pituitary-Thyroid (HPT) axis, increasing synthesis and release of hypothalamic-TRH, pituitary-TSH, and thyroid hormones T4 and T3; T4 in concert with NE induce brown adipose tissue (BAT) thermogenesis through stimulation of deiodinase 2 (Dio2), and uncoupling protein 1 (Ucp1) expression. These changes are detected within the first hour in male rats [J Neuroendo 12:861, 2014] while in females, only in ovariectomized [J Neuroendocrinol 21:439, 2009]. Given the thermogenic effect of ovarian hormones, we hypothesized that females could respond to longer exposures. Female Wistar rats were exposed individually to 5°C for 1 to 5h and compared to male’s acute response (15 min to 4h); controls were moved individually to a nearby room at 22°C for similar times. Rats were euthanized by guillotine, rectal temperature was immediately measured, trunk blood collected, serum separated, and tissues kept at -70°C. Hormone concentrations were quantified in serum by RIA and ELISA, and gene expression in paraventricular nucleus (PVN), anterior pituitary (AP), and BAT by RT-PCR or qPCR. Body temperature of cold-exposed males was higher than isolated controls since the first 30min, Trh expression increased at 1h in the paraventricular nucleus (PVN), TSH release from 15 min up to 2 hours, T4 levels peaked until 4h, and T3 increased after 2h as in [Endocrinology 58:140, 1993]; Trhr1 in AP reached its lowest levels at 2h. In BAT, Dio2 expression peaked at 1h and subsequently decreased. Ucp1 increased from 30 min and remained elevated until 4h, Adrb3, and Ppargc1a expressions were highest at 4h. Cold exposure in females decreased body temperature after 4 hours when Trh PVN expression increased and that of TRH receptor 1 (Trhr1) in AP was lowest; TRH degrading enzyme (Trhde) expression peaked after 2h of cold and subsequently decreased at 4h. TSH in serum increased at 2h and then returned to control levels, T4 slightly increased at 3h, and T3 peaked at 5h. Progesterone serum concentration increased from 2h and peaked at 4h. No changes were found in estradiol serum concentration. In BAT, Dio2 expression increased from 2 to 4h, Ucp1 at 3 and 5h while that of β3 adrenergic receptor (Adrb3) decreased at 2h but rose reaching a peak at 4h. In contrast, expression of Pgc1α -the major transcriptional coactivator of Ucp1- rapidly increased (1h) decreasing afterward. The data suggest that when the ambient temperature decreases, the sympathetic system is activated including stimulation of progesterone, and supports a delayed response of female HPT axis to cold exposure, compared to male’s leading to the proposal that when female body temperature diminishes, the HPT axis and thyroid hormone-induced thermogenesis are activated.Funding: DGAPA IN217422, PAEP, CONAHCYT 790605. Presentation: 6/2/2024

8515 Role of Insulin Receptor in Trpv1-positive Adipocyte Progenitor Cellsin Adipocyte Differentiation and Metabolic Function

Abstract Disclosure: C. Sahin: None. H. Camara: None. F. Shamsi: None. M. Lynes: None. Y. Tseng: None. Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, is an important endocrine organ in the regulation of energy balance. Stimulating BAT activation and beiging of white adipose tissue (WAT) are new strategies to combat metabolic diseases, such as obesity and diabetes. Traditionally, thermogenic adipocytes are known to originate from mesenchymal Pdgfrα-expressing adipocyte progenitor cells (APCs). A previous study conducted by our lab identified vascular smooth muscle cells as a novel cellular origin of APCs. These cells are characterized by the expression of transient receptor potential cation channel subfamily V member 1 (Trpv1+). With cold exposure, the Trpv1+ APC-derived adipocytes are increased in BAT and WAT and differentiated into highly thermogenic adipocytes. These findings indicate that the Trpv1+-APCs may play an important role in the development of brown and beige adipocytes in response to cold. This study was designed to explore the function of the Trpv1+ APC-derived adipocytes in thermogenic adipocyte differentiation and metabolic regulation. We generated a mouse model in which insulin receptor (IR), a well-known player in adipocyte differentiation, was deleted in the Trpv1+ APCs to impair their adipogenic potential. Trpv1-Cre::mTmG::IRflox transgenic and IRwt control mice were housed at cold temperature (5°C) for 7 days. Because the lineage tracing mTmG system was included, we were able to trace the fate of Trpv1+ APCs in the presence or absence of IR. We first examined the adipogenic capacity of the IR-deficient Trpv1+ cells in BAT and WAT tissues using whole-mounted adipose tissue imaging. In control mice, approximately 30% of all mature adipocytes were derived from Trpv1+ APCs in adipose tissue in response to cold. With ablation of IR in Trpv1+ APCs, this contribution was significantly reduced in BAT (by 11.7 % in females; 6.1% in males), inguinal WAT (by 16.8% in females; 19.3% males), and perigonadal WAT (by 11.4% in females; 14.8% in males) in transgenic mice compared to control mice. These results showed that IR-deficiency in the Trpv1-expressing cells impaired their adipogenesis in both male and female mice. In contrast, thermogenic genes (e.g., Ucp1, Pparγc1a, Cox7a1) were not significantly altered in BAT and inguinal WAT of the IR-deficient Trpv1+ APCs mice. Despite the changes in the adipocyte populations, we observed that deletion of IR in Trpv1+ APCs has no impact on body weight, food intake, fat mass, glucose tolerance, and insulin sensitivity relative to control mice. Taken together, blocking the contribution of Trpv1+ APCs to the mature adipocyte population results in no metabolic changes in mice, suggesting that the other APCs, such as PdgfRα+ APCs, may potentially compensate for impaired adipogenesis in different adipose tissues. Presentation: 6/1/2024

Biomimetic Single-Atom Nanozyme for Dual Starvation-Enhanced Breast Cancer Immunotherapy.

Cold exposure (CE) therapy is an innovative and cost-efficient cancer treatment that activates brown adipose tissue to compete for glucose uptake, leading to metabolic starvation in tumors. Exploring the combined antitumor mechanisms of CE and traditional therapies (such as nanocatalysis) is exciting and promising. In this study, a platelet membrane biomimetic single-atom nanozyme (SAEs) nanodrug (PFB) carrying bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide (BPTES) is developed for use in cancer CE therapy. Owing to the platelet membrane modification, PFB can effectively target tumors. Upon entering cancer cells, the dual starvation effect induced by CE treatment and BPTES can significantly diminish intracellular glucose and ATP levels, resulting in a substantial reduction in cellular (glutathione) GSH, which can enhance the cytotoxic efficacy of reactive oxygen species generated by SAEs. This strategy not only boosts ROS production in tumors, but also strengthens immune responses, particularly by increasing memory T-cell abundance and suppressing distant tumor growth and tumor metastasis. Compared with SAEs therapy alone, this combined approach offers superior benefits for tumor immunotherapy. This study achieves a combination of CE and nanomedicines for the first time, providing new ideas for future nanomedicine combination therapy modalities.

Case Study of Severe Accidental Hypothermia with Rapid Cooling, Preserved Shivering, and Consciousness with a Summary of Similar Case Reports.

We describe a case of severe accidental hypothermia of a kayaker with preserved consciousness and shivering despite a rectal temperature of 22.9°C following a 50-min immersion in 3°C water with an estimated core temperature cooling rate of 10.6°C/h. Based on survival at sea prediction curves and cooling rates from physiology studies, cold water (eg, 0-5°C) immersion is expected to drop core temperature by 2 to 4°C/h. Furthermore, accidental hypothermia classification systems predict that severely hypothermic patients are usually unconscious and not shivering. The patient in this report rewarmed rapidly at 3.6°C/h with only minimally invasive measures and was discharged fully neurologically intact. In 41 similar cases of survival in moderate to severe hypothermia with core temperatures <32°C due to cold water immersion, cold air exposure, or avalanche burial, mean cooling rates were 4.3±3.3°C/h (range 0.4-10.6°C/h). Including the current patient, shivering was reported in only four cases. We found several other cases of rewarming from moderate to severe hypothermia with only minimally invasive measures. The current and summarized cases lead us to conclude that patients may be at risk of severe hypothermia in <60 min of cold water immersion and that it is possible for severely hypothermic patients to have preserved consciousness, close to normal vital signs, and shivering. Minimally invasive or noninvasive rewarming of patients with severe hypothermia is also possible, especially in those who continue to shiver. Hypothermia management should not necessarily be guided by classification systems or core temperature alone but rather by a careful consideration of the entire clinical picture.

Sex-specific response of the human plasma lipidome to short-term cold exposure

Cold-induced lipolysis is widely studied as a potential therapeutic strategy to combat metabolic disease, but its effect on lipid homeostasis in humans remains largely unclear. Blood plasma comprises an enormous repertoire in lipids allowing insights into whole body lipid homeostasis. So far, reported results originate from studies carried out with small numbers of male participants. Here, the blood plasma's lipidome of 78 male and 93 female volunteers, who were exposed to cold below the shivering threshold for 2 h, was quantified by comprehensive lipidomics using high-resolution mass spectrometry. Short-term cold exposure increased the concentrations in 147 of 177 quantified circulating lipids and the response of the plasma's lipidome was sex-specific. In particular, the amounts of generated glycerophospholipid and sphingolipid species differed between the sexes. In women, the BMI could be related with the lipidome's response. A logistic regression model predicted with high sensitivity and specificity whether plasma samples were from male or female subjects based on the cold-induced response of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) species.In summary, cold exposure promotes lipid synthesis by supplying fatty acids generated after lipolysis for all lipid classes. The plasma lipidome, i.e. PC, LPC and SM, shows a sex-specific response, indicating a different regulation of its metabolism in men and women. This supports the need for sex-specific research and avoidance of sex bias in clinical trials.

The application of heating film to hands reduces the decline in manual dexterity performance associated with cold exposure.

Exposure to cold temperatures decreases finger temperature (Tfing) and dexterity. Decreased manual function and dexterity can be serious safety risks, especially in tasks that require fine motor movements that must be performed outdoors. The aim of this study was to determine whether hand heating with a minimal power requirement (14.8W) results in a smaller reduction in Tfing and manual dexterity performance during mild cold exposure compared to a non-heated control condition. In a randomized crossover design, twenty-two healthy participants were exposed to a moderately cold environment (5 ºC) for 90min. One condition had no intervention (CON), while the other had the palmar and dorsal hands heated (HEAT) by using electric heating films. Tfing and cutaneous vascular conductance (CVC) were continuously monitored using laser Doppler flowmetry. Manual dexterity performance and cognitive function were assessed by the Grooved Pegboard Test (GPT) and Stroop Color-Word (SCW) test, respectively, during the baseline period and every 30min during the cold exposure. After the cold exposure, Tfing was higher in HEAT relative to CON (CON 9.8 vs. HEAT 13.7ºC, p < 0.0001). GPT placing time, as an index of dexterity performance, was also shorter in HEAT by 14.5% (CON 69.10 ± 13.08 vs. HEAT 59.06 ± 7.99s, p < 0.0001). There was no difference in CVC between the two conditions during the cold exposure (p > 0.05 for all). Cognitive function was similar between two conditions (p > 0.05 for all). The proposed hand heating method offers a practical means of heating fingers to maintain dexterity throughout prolonged cold exposure.

Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM. The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot. CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect. Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

Hot and cold exposure triggers distinct transcriptional and behavioral responses in laboratory-inbred pond snails

Animals exhibit remarkable behavioral and molecular adaptations to cope with thermal stressors, which are crucial for survival in variable environments that are exacerbated by climate change. Aquatic poikilotherms like our model organism—the pond snail Lymnaea stagnalis—face significant challenges due to their dependence on external temperatures. Our study provides valuable insights into the different behavioral and molecular responses of lab-inbred snails to cold and heat shock stressors (i.e., 4 °C and 30 °C), particularly in the context of learning and memory formation. We found that while short-term (1 h) cold exposure transiently upregulated the expression levels of HSP70 and HSP40 in the snail’s central ring ganglia, prolonged cold exposure (24 h) resulted in a significant downregulation of LymMIPII and an upregulation of LymMIPR. These data suggest, albeit at the transcriptional level, the existence of a negative feedback loop necessary for sustaining cellular functions when metabolic demands might shift towards conserving energy during prolonged cold exposure. At the behavioral level, we found that, compared to heat shock, cold exposure did not result in a Garcia effect (i.e., a “special form” of conditioned taste aversion). The difference in memory outcomes was associated with changes in the expression levels of selected targets involved in neuronal plasticity and the stress response. While both cold and heat shock upregulated the HSP levels in the snail's central ring ganglia, cold exposure did not affect the expression levels of the neuroplasticity genes LymGRIN1 and LymCREB1, contrasting with heat shock’s neurogenic effects. Overall, this study provides insights into L. stagnalis's adaptive responses to thermal stressors, emphasizing different molecular strategies for coping with heat versus cold challenges in aquatic environments. These findings contribute to our understanding of thermal biology and stress physiology in aquatic organisms, underscoring the importance of molecular mechanisms in shaping species' resilience in dynamic environments.

Sex differences in physiological responses and thermal perception during repeated extremely cold exposure (−15 °C)

People working in cold regions often need to move frequently between indoor and outdoor environments. Due to sex differences in metabolic rates and thermal sensitivity, repeated exposure to large temperature differences may stress physiological and perceptual systems of males and females differently. This study aims to explore the physiological responses and thermal perception changes in males and females repeatedly exposed to −15 °C. The experiment involved 20 participants (gender balanced), who experienced two consecutive cycles of cold exposure. Each cycle included 30 min of cold exposure and 30 min of recovery. During the experiment, multiple physiological parameters as well as overall and local thermal perception were recorded. The experimental results indicate that repeated cold exposure can lead to thermal habituation in both males and females. Males exhibited higher skin temperatures in extremities such as the hands, fingers, face, and feet, while females reported lower thermal sensations in these areas during the recovery period. Furthermore, repeated cold exposure has a greater impact on the rate of recovery of extremity skin temperatures in females, requiring a longer recovery time compared to males. This article has reference value for considering sex differences in the design of temporary transition spaces in winter, which is beneficial to improving thermal comfort and energy efficiency.

Association of brown adipose tissue activity with circulating sex hormones and fibroblast growth factor 21 in the follicular and luteal phases in young women

BackgroundThermogenesis is influenced by fluctuations in sex hormones during the menstrual cycle in premenopausal women. The thermogenic activity and mass of brown adipose tissue (BAT) are regulated by endocrine factors, including sex hormones and fibroblast growth factor 21 (FGF21). However, the relationship between human BAT and these endocrine fluctuations within individuals remains to be elucidated. This study aimed to assess variations in BAT activity between the luteal and follicular phases and identify correlations with circulating levels of sex hormones and FGF21.MethodsHealthy young women were enrolled in an observational study. Measurement of BAT activity and blood analyses were performed in both the follicular and luteal phases. BAT activity was analyzed using thermography with 2-h cold exposure. Plasma 17β-estradiol, progesterone, and FGF21 levels were determined by enzyme-linked immunosorbent assay. A comparative analysis within individuals was conducted in 13 women to compare the follicular and luteal phases. Furthermore, sensitivity analysis was carried out in 21 women during the follicular phase only.ResultsPlasma 17β-estradiol and progesterone levels were significantly higher in the luteal phase, whereas plasma FGF21 level was significantly higher in the follicular phase. Comparison analysis found no significant differences in cold-induced BAT activity between the follicular and luteal phases in young women. Correlation analysis in both comparison and sensitivity analyses found that plasma 17β-estradiol and progesterone levels were not associated with BAT activity, whereas plasma FGF21 levels were significantly and positively correlated with BAT activity only in the follicular phase. In addition, plasma 17β-estradiol levels in the follicular phase were significantly and positively associated with plasma FGF21 levels in both the comparison and sensitivity analyses.ConclusionsThe thermogenic activity of BAT during cold exposure was comparable between the follicular and luteal phases in young women. Higher BAT activity was associated with elevated levels of plasma FGF21 only in the follicular phase, which is related to increased plasma 17β-estradiol levels.