24-h passive heat and cold exposures did not modify energy intake and appetite but strongly modify food reward.

Effects of acute thermal exposures on appetite appear hypothetical in reason of very heterogeneous methodologies. The aim of this study was therefore to clearly define the effects of passive 24-h cold (16°C) and heat (32°C) exposures on appetitive responses compared to a thermo neutral condition (24°C). Twenty-three healthy, young, and active male participants realised three sessions (from 1 pm) in a laboratory conceived like an apartment dressed with the same outfit (Clo=1). Three meals composed of three or four cold or warm dishes were served ad libitum to assess energy intake (EI). Leeds Food Preference Questionnaires were used before each meal to assess food reward. Subjective appetite was regularly assessed and levels of appetitive hormones (acylated ghrelin, GLP-1, leptin, and PYY) were assessed before and after the last meal (lunch). Contrary to the literature, total EI was not modified by cold or heat exposure (p=0.120). Accordingly, hunger scores (p=0.554) were not altered. Levels of acylated ghrelin and leptin were marginally higher during the 16 (p=0.032) and 32°C (p<0.023) sessions, respectively. Interestingly, implicit wanting for cold and low-fat foods at 32°C and for warm and high-fat foods at 16°C were increased during the whole exposure (p < 0.024). Moreover, cold entrées were more consumed at 32 °C (p<0.062) and warm main dishes more consumed at 16°C (p<0.025). Thus, passive cold and hot exposures had limited effects on appetite and it seems that offering some choice based on food temperature may help individuals to express their specific food preferences and maintain EI.

Circulating microRNA levels after exercise-induced muscle damage and the repeated bout effect.

The neuromuscular system can quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). Circulating muscle-specific microRNAs (myomiRs) may be able to potentially predict the long-lasting maximal voluntary contraction (MVC) torque deficit (>24 h), an indicator of EIMD. We aimed to investigate: 1) how plasma myomiR levels are modified by the RBE and 2) whether plasma myomiRs can predict the long-lasting MVC torque deficit. Nineteen participants performed two identical bouts of loaded downhill walking separated by 2 wk. MVC torque, creatine kinase (CK) activity, myoglobin (Mb) concentration, and myomiR levels were measured before and up to 48 h after exercise. Correlation and multiple regression analyses were performed to assess the ability of these markers to predict the largest MVC torque loss beyond 24 h postexercise. Similar to MVC torque, CK activity, and the Mb concentration, the relative abundance of certain myomiRs (hsa-miR-1-3p, and hsa-miR-133a-3p) was less affected after the second bout of exercise relative to the first bout. The CK activity, Mb concentration, and level of several myomiRs (hsa-miR-1-3p, hsa-miR-133a-3p, and hsa-miR-206) correlated with long-lasting MVC torque loss. Multiple regression showed that the best combination of markers to predict the long-lasting deficit of MVC torque included several myomiRs, Mb, and CK. Certain myomiR levels increased less after exercise bout 2 than after exercise bout 1, indicating the presence of the RBE. The measurement of myomiR levels in combination with Mb concentrations and CK activity could improve the prediction of the long-lasting MVC torque deficit.NEW & NOTEWORTHY The present study is the first to show that plasma muscle-specific microRNA (myomiR) levels can be modified by the repeated bout effect, as their levels increased less after the second exercise bout relative to the first. This study is also the first to suggest that myomiR levels could be used to partially predict maximal voluntary contraction torque loss at 24 h postexercise (i.e., the magnitude of exercise-induced muscle damage). Interestingly, the combined measurement of certain myomiR levels with those of myoglobin and creatine kinase improved the predictive value.

Impact of the Rapid Normalization of Chronic Hyperglycemia on the Receptor Activator of Nuclear Factor-Kappa B Ligand and the Osteoprotegerin System in Patients Living with Type 2 Diabetes: RANKL-GLYC Study.

The RANKL-GLYC study aims to explore the impact of the rapid correction of chronic hyperglycemia on the receptor activator of nuclear factor-kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG). RANKL and OPG are considered the main factors in the pathophysiology of Charcot neuroarthropathy, a devastating complication of the joints that remains poorly understood. The study began recruiting patients in September 2021 and ends in June 2022; the final study results are scheduled for January 2023.

Circulating microRNAs after a 24-h ultramarathon run in relation to muscle damage markers in elite athletes.

Ultra-endurance sports are growing in popularity but can be associated with adverse health effects, such as exercise-induced muscle damage (EIMD), which can lead to exertional rhabdomyolysis. Circulating microRNAs (miRNAs) may be useful to approach the degree of EIMD. We aimed to (1) investigate the relevance of circulating miRNAs as biomarkers of muscle damage and (2) examine the acute response of skeletal/cardiac muscle and kidney biomarkers to a 24-h run in elite athletes. Eleven elite athletes participated in the 24-h run World Championships. Counter-movement jump (CMJ), creatine kinase (CK), myoglobin (Mb), creatinine (Cr), high-sensitive cardiac troponin T (hs-cTnT), and muscle-specific miRNA (myomiR) levels were measured before, immediately after, and 24 and 48h after the race. CMJ height was reduced immediately after the race (-84.0 ± 25.2%, p < 0.001) and remained low at 24 h (-43.6 ± 20.4%, p = 0.002). We observed high CK activity (53 239 ± 63 608 U/L, p < 0.001) immediately after the race, and it remained elevated 24h after (p < 0.01). Circulating myomiR levels (miR-1-3p, miR-133a-3p, miR-133b, miR-208a-3p, miR-208b-3p, and miR-499a-5p) were elevated immediately after the 24-h run (fold changes: 18-124,723, p<0.001) and significantly (p < 0.05) correlated or tended to significantly (p < 0.07) correlate with the reduction in CMJ height at 24 h. We found no significant correlation between CMJ height loss at 24 h and CK (p = 0.23) or Mb (p = 0.41) values. All elite ultramarathon runners included in our study were diagnosed with exertional rhabdomyolysis after the 24-h ultramarathon race. MyomiR levels may be useful to approach the degree of muscle damage.

Circulating miRNAs as Biomarkers of Acute Muscle Damage in Rats.

Skeletal muscle damage is an often-occurring event. Diagnosis using the classic blood marker creatine kinase sometimes yields unsatisfactory results due to great interindividual variability. Therefore, the identification of reliable biomarkers is important. Our aim was to detect and characterize circulating miRNAs in plasma in response to acute notexin-induced muscle damage in rats. Real-time quantitative RT-PCR profiling led to the identification of miRNAs that were highly increased in plasma in response to notexin injection into several muscles, namely miR-1-3p, -133a-3p, -133b-3p, -206-3p, -208b-3p, and -499-5p, as well as miR-378a-3p and miR-434-3p. Peak values of miRNAs appeared 12 hours after injury, and were contained both in the vesicular and nonvesicular fractions of plasma. Receiver operating characteristic curve analysis showed that circulating miRNAs could accurately discriminate between damaged and nondamaged tissues. Furthermore, we tested the robustness of expression profiles in slow- and fast-type fibers. Upon inducing damage in slow- or fast-type muscle, we found that the damaged-muscle phenotype had a very limited impact on the miRNA response. Similarly, the circulating miRNAs selected were not affected by hemolysis or platelets, two pre-analytical factors known to affect plasma miRNA profiles. Taken together, our results show that circulating muscle-specific miRNAs, miR-378a-3p and miR-434-3p, are robust and promising biomarkers of acute muscle damage in rats.

Plasmodium falciparum infection-induced changes in erythrocyte membrane proteins.

Over the past decade, advances in proteomic and mass spectrometry techniques and the sequencing of the Plasmodium falciparum genome have led to an increasing number of studies regarding the parasite proteome. However, these studies have focused principally on parasite protein expression, neglecting parasite-induced variations in the host proteome. Here, we investigated P. falciparum-induced modifications of the infected red blood cell (iRBC) membrane proteome, taking into account both host and parasite proteome alterations. Furthermore, we also determined if some protein changes were associated with genotypically distinct P. falciparum strains. Comparison of host membrane proteomes between iRBCs and uninfected red blood cells using fluorescence-based proteomic approaches, such as 2D difference gel electrophoresis revealed that more than 100 protein spots were highly up-represented (fold change increase greater than five) following P. falciparum infection for both strains (i.e. RP8 and Institut Pasteur Pregnancy Associated Malaria). The majority of spots identified by mass spectrometry corresponded to Homo sapiens proteins. However, infection-induced changes in host proteins did not appear to affect molecules located at the outer surface of the plasma membrane. The under-representation of parasite proteins could not be attributed to deficient parasite protein expression. Thus, this study describes for the first time that considerable host protein modifications were detected following P. falciparum infection at the erythrocyte membrane level. Further analysis of infection-induced host protein modifications will improve our knowledge of malaria pathogenesis.

Effect of heat acclimation on metabolic adaptations induced by endurance training in soleus rat muscle.

Aerobic training leads to well-known systemic metabolic and muscular alterations. Heat acclimation may also increase mitochondrial muscle mass. We studied the effects of heat acclimation combined with endurance training on metabolic adaptations of skeletal muscle. Thirty-two rats were divided into four groups: control (C), trained (T), heat-acclimated (H), and trained with heat acclimation (H+T) for 6 weeks. Soleus muscle metabolism was studied, notably by the in situ measurement of mitochondrial respiration with pyruvate (Pyr) or palmitoyl-coenzyme A (PCoA), under phosphorylating conditions ( V˙max ) or not ( V˙0 ). Aerobic performance increased, and retroperitoneal fat mass decreased with training, independently of heat exposure (p < 0.001 and p < 0.001, respectively). Citrate synthase and hydroxyl-acyl-dehydrogenase activity increased with endurance training (p < 0.001 and p < 0.01, respectively), without any effect of heat acclimation. Training induced an increase of the V˙0 and V˙max for PCoA (p < .001 and p < .01, respectively), without interference with heat acclimation. The training-induced increase of V˙0 (p < 0.01) for pyruvate oxidation was limited when combined with heat acclimation (-23%, p < 0.01). Training and heat acclimation independently increased the V˙max for pyruvate (+60% p < 0.001 and +50% p = 0.01, respectively), without an additive effect of the combination. Heat acclimation doubled the training effect on muscle glycogen storage (p < 0.001). Heat acclimation did not improve mitochondrial adaptations induced by endurance training in the soleus muscle, possibly limiting the alteration of carbohydrate oxidation while not facilitating fatty-acid utilization. Furthermore, the increase in glycogen storage observed after HA combined with endurance training, without the improvement of pyruvate oxidation, appears to be a hypoxic metabolic phenotype.

Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria.

BACKGROUND: Plasmodium falciparum infections could lead to severe malaria, principally in non-immune individuals as children and travellers from countries exempted of malaria. Severe malaria is often associated with the sequestration of P. falciparum-infected erythrocytes in deep micro-vascular beds via interactions between host endothelial receptors and parasite ligands expressed on the surface of the infected erythrocyte. Although, serological responses from individuals living in endemic areas against proteins expressed at surface of the infected erythrocyte have been largely studied, seldom data are available about the specific targets of antibody response from travellers. METHODS: In order to characterize antigens recognized by traveller sera, a comparison of IgG immune response against membrane protein extracts from uninfected and P. falciparum-infected red blood cells (iRBC), using immunoblots, was performed between non exposed individuals (n = 31) and briefly exposed individuals (BEI) (n = 38) to malaria transmission. RESULTS: Immune profile analysis indicated that eight protein bands from iRBC were significantly detected more frequently in the BEI group. Some of these antigenic proteins were identified by an original immuno-proteomic approach. CONCLUSION: Collectively, these data may be useful to characterize the singular serological immune response against a primary malaria infection in individuals briefly exposed to transmission.

The effect of a physiological increase in temperature on mitochondrial fatty acid oxidation in rat myofibers.

We investigated the effect of temperature increase on mitochondrial fatty acid (FA) and carbohydrate oxidation in the slow-oxidative skeletal muscles (soleus) of rats. We measured mitochondrial respiration at 35°C and 40°C with the physiological substrates pyruvate + 4 mM malate (Pyr) and palmitoyl-CoA (PCoA) + 0.5 mM malate + 2 mM carnitine in permeabilized myofibers under nonphosphorylating (V˙0) or phosphorylating (V˙max) conditions. Mitochondrial efficiency was calculated by the respiratory control ratio (RCR = V˙max/V˙0). We used guanosine triphosphate (GTP), an inhibitor of uncoupling protein (UCP), to study the mechanisms responsible for alterations of mitochondrial efficiency. We measured hydrogen peroxide (H2O2) production under nonphosphorylating and phosphorylating conditions at both temperatures and substrates. We studied citrate synthase (CS) and 3-hydroxyl acyl coenzyme A dehydrogenase (3-HAD) activities at both temperatures. Elevating the temperature from 35°C to 40°C increased PCoA-V˙0 and decreased PCoA-RCR, corresponding to the uncoupling of oxidative phosphorylation (OXPHOS). GTP blocked the heat-induced increase of PCoA-V˙0. Rising temperature moved toward a Pyr-V˙0 increase, without significance. Heat did not alter H2O2 production, resulting from either PCoA or Pyr oxidation. Heat induced an increase in 3-HAD but not in CS activities. In conclusion, heat induced OXPHOS uncoupling for PCoA oxidation, which was at least partially mediated by UCP and independent of oxidative stress. The classically described heat-induced glucose shift may actually be mostly due to a less efficient FA oxidation. These findings raise questions concerning the consequences of heat-induced alterations in mitochondrial efficiency of FA metabolism on thermoregulation.NEW & NOTEWORTHY Ex vivo exposure of skeletal myofibers to heat uncouples substrate oxidation from ADP phosphorylation, decreasing the efficiency of mitochondria to produce ATP. This heat effect alters fatty acids (FAs) more than carbohydrate oxidation. Alteration of FA oxidation involves uncoupling proteins without inducing oxidative stress. This alteration in lipid metabolism may underlie the preferential use of carbohydrates in the heat and could decrease aerobic endurance.

Circulating levels of non-muscle-specific miRNAs in response to acute muscle damage in rat.

MicroRNA (miRNA) are found in numerous biofluids including blood and are considered a new class of biomarkers. In several animal models as well as in human diseases, they are interesting circulating markers of acute or chronic tissue injury. This article provides additional data related to a previous research article entitled "Circulating miRNAs as biomarkers of acute muscle damage in rats" by Siracusa et al. (2016) [1]. The data were obtained by RT-qPCR performed on plasma of rats exposed to acute muscle damage. The present set of data displays 45 non muscle-specific miRNA responses to acute, experimental muscle injury in healthy rats. They complement previous findings showing that circulating levels of miRNAs can be affected by muscle damage.

Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage.

Skeletal muscle is a heterogeneous tissue composed of a continuum of contracting fibers ranging from slow-type to fast-type fibers. Muscle damage is a frequent event and a susceptibility of fast-fibers to exercise-induced damage (EIMD) or statins toxicity has been reported. Biological markers of muscle damage such as creatine kinase (CK) are not fiber-type specific and new biomarkers are needed. Some microRNAs (miRNAs) are specific to the muscle tissue, can be found in the extracellular compartment and can rise in the plasma following muscle damage. Our aim was to identify whether a set of circulating miRNAs can be used as fiber-type specific biomarkers of muscle damage in a model of traumatic (crush) injuries induced either in the slow soleus (SOL) or in the fast extensor digitorum longus (EDL) muscles of rats. A subset of miRNAs composed of miR-1-3p, -133a-3p, -133b-3p, 206-3p, -208b-3p, 378a-3p, -434-3p, and -499-5p were measured by RT-PCR in non-injured SOL or EDL muscle and in the plasma of rats 12 h after damage induced to SOL or EDL. MiR-133b-3p, -378a-3p, and -434-3p were equally expressed both in SOL and EDL muscles. MiR-1-3-p and -133a-3p levels were higher in EDL compared to SOL (1.3- and 1.1-fold, respectively). Conversely, miR-206-3p, -208b-3p, and -499-5p were mainly expressed in SOL compared to EDL (7.4-, 35.4-, and 10.7-fold, respectively). In the plasma, miR-1-3p and -133a-3p were elevated following muscle damage compared to a control group, with no difference between SOL and EDL. MiR-133b-3p and -434-3p plasma levels were significantly higher in EDL compared to SOL (1.8- and 2.4-fold, respectively), while miR-378a-3p rose only in the EDL group. MiR-206-3p levels were elevated in SOL only (fourfold compared to EDL). Our results show that plasma miR-133b-3p and -434 are fast-fiber specific biomarkers, while miR-206-3p is a robust indicator of slow-fiber damage, opening new perspectives to monitor fiber-type selective muscle damage in research and clinic.

Short-Term, Low-Volume Training Improves Heat Acclimatization in an Operational Context.

Personnel who travel to areas with a hot climate (WBGT > 27°C) may suffer from the heat (physiological strain, thermal discomfort, increased probability of heat illness), making them partially or fully inoperative. Performing physical activities during heat acclimatization is known to improve this process (i.e., improve measures of acclimatization for the same duration of acclimation). However, it is unknown whether such training would be efficient in an operative context, characterized by a high volume of work-related physical activity. Thirty French soldiers (Training group, T) performed a short (5 days), progressive, moderate (from three to five 8-min running sets at 50% of the speed at VO2max for 32-56 min) aerobic training program upon arriving at their base in United Arab Emirates (~40°C and 12% RH). A control group (30 soldiers; No Training, NT) continued to perform their usual outdoor military activities (~6 h.d-1). A field heat stress test (HST; three 8-min running sets at 50% of the speed at VO2max) was performed, before and after the heat acclimatization period, to assess physiological and subjective changes. Rectal temperature, heart rate (HR), thermal discomfort at rest and at the end of exercise, rates of perceived exertion (RPE), and sweat loss and osmolality decreased following heat acclimatization in both groups. However, the decreases in the T group were larger than those in the NT group for HR at the end of exercise (-20 ± 13 vs. -13 ± 6 bpm, respectively, p = 0.044), thermal discomfort at rest (-2.6 ± 2.7 vs. -1.4 ± 2.1 cm, respectively, p = 0.013) and at the end of exercise (-2.6 ± 1.9 vs. -1.6 ± 1.7 cm, respectively, p = 0.037) and RPE (-2.3 ± 1.8 vs. -1.3 ± 1.7, respectively, p = 0.035). Thus, we showed that adding short (<60 min), daily, moderate-intensity training sessions during a professional mission in a hot and dry environment accelerated several heat-acclimatization-induced changes at rest and during exercise in only 5 days.

Hepatocyte pathway alterations in response to in vitro Crimean Congo hemorrhagic fever virus infection.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus responsible for hemorrhagic manifestations and multiple organ failure, with a high mortality rate. In infected humans, damage to endothelial cells and vascular leakage may be a direct result of virus infection or an immune response-mediated indirect effect. The main target cells are mononuclear phagocytes, endothelial cells and hepatocytes; the liver being a key target for the virus, which was described as susceptible to interferon host response and to induce apoptosis. To better understand the early liver cell alterations due to virus infection, the protein profile of in vitro CCHFV-infected HepG2 cells was analyzed using two quantitative proteomic approaches, 2D-DIGE and iTRAQ. A set of 243 differentially expressed proteins was identified. Bioinformatics analysis (Ingenuity Pathways Analysis) revealed multiple host cell pathways and functions altered after CCHFV infection, with notably 106 proteins related to cell death, including 79 associated with apoptosis. Different protein networks emerged with associated pathways involved in inflammation, oxidative stress and apoptosis, ubiquitination/sumoylation, regulation of the nucleo-cytoplasmic transport, and virus entry. Collectively, this study revealed host liver protein abundances that were modified at the early stages of CCHFV infection, offering an unparalleled opportunity of the description of the potential pathogenesis processes and of possible targets for antiviral research.

Salivary gland protein repertoire from Aedes aegypti mosquitoes.

Diseases caused by arthropod-borne viruses are a significant threat to the health of human and animal populations throughout the world. Better knowledge of the molecules synthesized in the salivary gland and saliva of hematophagous arthropods could be of use for improving the control of pathogen transmission. Recently, a sialome analysis of three Aedes aegypti mosquito colonies (PAEA, Rockefeller, and Formosus) carried out in our laboratory allowed us to identify 44 saliva proteins. Of these secreted proteins, none was exclusively expressed in one colony, suggesting that expression of salivary proteins is highly conserved across populations. In another study, we reported that some of these salivary proteins could be used as the genus-specific markers for travelers' exposure to mosquito vectors. Here, comparison of salivary gland protein profiles between these same three Ae. aegypti colonies was performed using the one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) difference gel electrophoresis method. As observed at the saliva level, no significant differences were detected between these three colonies. The salivary gland protein repertoire from the Ae. aegypti mosquito was analyzed using a proteomic approach. One hundred and twenty proteins were identified in these salivary glands representing the largest description of the Ae. aegypti salivary gland protein catalog. We succeeded in identifying 15 secreted proteins, some of which have already been reported as being involved in blood feeding. A comparison of the proteins identified between the salivary glands and the sialome is discussed.