Regular exercise stimulates endothelium autophagy via IL-1 signaling in ApoE deficient mice.

Regular exercise maintains arterial endothelial cell homeostasis and protects the arteries from vascular disease, such as peripheral artery disease and atherosclerosis. Autophagy, which is a cellular process that degrades misfolded or aggregate proteins and damaged organelles, plays an important role in maintaining organ and cellular homeostasis. However, it is unknown whether regular exercise stimulates autophagy in aorta endothelial cells of mice prone to atherosclerosis independently of their circulating lipid profile. Here, we observed that 16 weeks of voluntary exercise reduced high-fat diet-induced atherosclerotic plaque formation in the aortic root of ApoE deficient mice, and that this protection occurred without changes in circulating triglycerides, total cholesterol, and lipoproteins. Immunofluorescence analysis indicated that voluntary exercise increased levels of the autophagy protein LC3 in aortic endothelial cells. Interestingly, human umbilical vein endothelial cells (HUVECs) exposed to serum from voluntarily exercised mice displayed significantly increased LC3-I and LC3-II protein levels. Analysis of circulating cytokines demonstrated that voluntary exercise caused changes directly relevant to IL-1 signaling (ie, decreased interleukin-1 receptor antagonist [IL-1ra] while also increasing IL-1α). HUVECs exposed to IL-1α and IL-1ß recombinant protein significantly increased LC3 mRNA expression, LC3-I and LC3-II protein levels, and autophagy flux. Collectively, these results suggest that regular exercise protects arteries from ApoE deficient mice against atherosclerosis at least in part by stimulating endothelial cell autophagy via enhanced IL-1 signaling.

Influence of exogenous and endogenous estrogen on thermoregulatory responses to mild heat and the interaction with light and dark phases.

The present study aimed to determine the influence of estradiol (E2) and the interaction with circadian phases on thermoregulatory responses to mild heat in female rats. Heat loss and production during 3-h exposure to the environment at an ambient temperature of 28-34 °C were assessed by measuring abdominal temperature (Tabd), tail skin temperature, and oxygen consumption in ovariectomized rats with and without E2 replacement (OVX + E2 and OVX, respectively) and in control rats in the proestrus (P) and diestrus (D) phases. In the light phase, Tabd remained unchanged in all groups. Tabd increased in the dark phase, but was lower in the OVX + E2 and P groups than in the OVX and D groups. Oxygen consumption decreased at 34 °C, but to a lesser extent in the OVX + E2 group than in the OVX group. These results suggest that E2 activates thermoregulation in mild heat in the dark phase.

Muscle-derived SDF-1α/CXCL12 modulates endothelial cell proliferation but not exercise training-induced angiogenesis.

Chemokines are critical mediators of angiogenesis in several physiological and pathological conditions; however, a potential role for muscle-derived chemokines in exercise-stimulated angiogenesis in skeletal muscle remains poorly understood. Here, we postulated that the chemokine stromal cell-derived factor-1 (SDF-1α/C-X-C motif chemokine ligand 12: CXCL12), shown to promote neovascularization in several organs, contributes to angiogenesis in skeletal muscle. We found that CXCL12 is abundantly expressed in capillary-rich oxidative soleus and exercise-trained plantaris muscles. CXCL12 mRNA and protein were also abundantly expressed in muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α transgenic mice, which have a high proportion of oxidative muscle fibers and capillaries when compared with wild-type littermates. We then generated CXCL12 muscle-specific knockout mice but observed normal baseline capillary density and normal angiogenesis in these mice when they were exercise trained. To get further insight into a potential CXCL12 role in a myofiber-endothelial cell crosstalk, we first mechanically stretched C2C12 myotubes, a model known to induce stretch-related chemokine release, and observed increased CXCL12 mRNA and protein. Human umbilical vein endothelial cells (HUVECs) exposed to conditioned medium from cyclically stretched C2C12 myotubes displayed increased proliferation, which was dependent on CXCL12-mediated signaling through the CXCR4 receptor. However, HUVEC migration and tube formation were unaltered under these conditions. Collectively, our findings indicate that increased muscle contractile activity enhances CXCL12 production and release from muscle, potentially contributing to endothelial cell proliferation. However, redundant signals from other angiogenic factors are likely sufficient to sustain normal endothelial cell migration and tube formation activity, thereby preserving baseline capillary density and exercise training-mediated angiogenesis in muscles lacking CXCL12.

Thermal and cardiovascular responses and thermal sensation during hot-water bathing and the influence of room temperature.

The aim of the present study was to clarify physical risks during hot-water bathing by measuring thermal and cardiovascular responses and thermal sensation. Young men and women (n = 7 and 5, respectively) participated in the present study, which consisted of two trials mimicking bathing behavior at room temperature of 25 °C and 15 °C. Participants bathed in 41 °C water for 20 min to the subclavian level. Before bathing, participants rested fully clothed for 15 min and then rested for 15 min without clothes. After bathing, they rested without clothes for 15 min and afterwards rested fully clothed for another 15 min. Tympanic temperature (Tty), heart rates (HR), mean skin temperature (Tsk), mean arterial pressure (MAP), and laser-Doppler flow at the chest and forehead (LDFhead and LDFchest) were evaluated. Thermal perception was assessed with a visual analogue scale. Mean Tsk in the 15 °C trial decreased during the period without clothing while MAP increased. The value remained unchanged in the 25 °C trial. During bathing, Tty, mean Tsk, HR, LDFhead, and LDFchest increased in both trials, and MAP decreased to similar levels. Relative change in LDFchest was greater in the 15 °C trial than in the 25 °C trial. Participants felt cold when they were without clothes at 15 °C; however, the thermal perception during bathing was similar between the two trials. Greater changes in cardiovascular and thermal responses were observed during the bathing behavior. In addition, bathing in cold room augmented the changes, which may induce some physical risks during bathing.

Thermal comfort.

The processes of thermoregulation are roughly divided into two categories: autonomic and behavioral. Behavioral thermoregulation alone does not have the capacity to regulate core temperature, as autonomic thermoregulation. However, behavioral thermoregulation is often utilized to maintain core temperature in a normal environment and is critical for surviving extreme environments. Thermal comfort, i.e., the hedonic component of thermal perception, is believed to be important for initiating and/or activating behavioral thermoregulation. However, the mechanisms involved are not fully understood. Thermal comfort is usually obtained when thermal stimuli to the skin restore core temperature to a regulated level. Conversely, thermal discomfort is produced when thermal stimuli result in deviations of core temperature away from a regulated level. Regional differences in the thermal sensitivity of the skin, hypohydration, and adaptation of the skin may affect thermal perception. Thermal comfort and discomfort seem to be determined by brain mechanisms, not by peripheral mechanisms such as thermal sensing by the skin. The insular and cingulate cortices may play a role in assessing thermal comfort and discomfort. In addition, brain sites involved in decision making may trigger behavioral responses to environmental changes.

Assessment of axillary temperature for the evaluation of normal body temperature of healthy young adults at rest in a thermoneutral environment.

BACKGROUND: The aims of this study were to (1) evaluate whether recently introduced methods of measuring axillary temperature are reliable, (2) examine if individuals know their baseline body temperature based on an actual measurement, and (3) assess the factors affecting axillary temperature and reevaluate the meaning of the axillary temperature. METHODS: Subjects were healthy young men and women (n = 76 and n = 65, respectively). Three measurements were obtained: (1) axillary temperature using a digital thermometer in a predictive mode requiring 10 s (T ax-10 s), (2) axillary temperature using a digital thermometer in a standard mode requiring 10 min (T ax-10 min), and (3) tympanic membrane temperature continuously measured by infrared thermometry (T ty). The subjects answered questions about eating and exercise habits, sleep and menstrual cycles, and thermoregulation and reported what they believed their regular body temperature to be (T reg). RESULTS: T reg, T ax-10 s, T ax-10 min, and T ty were 36.2 ± 0.4, 36.4 ± 0.5, 36.5 ± 0.4, and 36.8 ± 0.3 °C (mean ± SD), respectively. There were correlations between T ty and T ax-10 min, T ty and T ax-10 s, and T ax-10 min and T ax-10 s (r = .62, r = .46, and r = .59, respectively, P < .001), but not between T reg and T ax-10 s (r = .11, P = .20). A lower T ax-10 s was associated with smaller body mass indices and irregular menstrual cycles. CONCLUSIONS: Modern devices for measuring axillary temperature may have changed the range of body temperature that is recognized as normal. Core body temperature variations estimated by tympanic measurements were smaller than those estimated by axillary measurements. This variation of axillary temperature may be due to changes in the measurement methods introduced by modern devices and techniques. However, axillary temperature values correlated well with those of tympanic measurements, suggesting that the technique may reliably report an individual's state of health. It is important for individuals to know their baseline axillary temperature to evaluate subsequent temperature measurements as normal or abnormal. Moreover, axillary temperature variations may, in part, reflect fat mass and changes due to the menstrual cycle.

Cold exposure and/or fasting modulate the relationship between sleep and body temperature rhythms in mice.

We assessed the relationship between core temperature (Tc) and sleep rhythms in mice, and examined the effects of ambient temperature and fasting. Tc, electroencephalograms (EEG), electromyograms (EMG), and spontaneous activity in male ICR mice (n=9) were measured by telemetry for 3 days under a 12:12h dark-light cycle. Mice were fed or fasted at an ambient temperature (Ta) of 27°C or 20°C for the final 30h of the experiment. The vigilance state was categorized into a wake state, rapid-eye movement (REM) sleep, and non-REM (NREM) sleep, and the total sleep time (TST) was assessed. Relationships between Tc and TST, NREM periods, and REM sleep were estimated using Pearson's correlation coefficient. During cold exposure, Tc decreased during the dark and light phases, and TST and the periods of NREM and REM sleep decreased during the dark phase. Throughout the fasting period, Tc also decreased during the dark and light phases. Furthermore, the decrease in Tc was augmented when fasting and cold were combined. TST and NREM sleep periods decreased in the light and dark phases, respectively, whereas REM sleep periods decreased in both phases. Negative linear correlations (r=-0.884 to -0.987) were observed between Tc and TST, NREM sleep periods, and REM sleep periods, except for Tc and REM sleep periods where fasting and cold conditions were combined. The correlations between sleep and Tc rhythms were well maintained during cold exposure and fasting. However, when cold and fasting were combined, REM sleep and Tc rhythms were desynchronized.