Aerobic endurance training status affects lymphocyte apoptosis sensitivity by induction of molecular genetic adaptations.

Apoptosis is a genetically regulated form of programmed cell death which promotes the elimination of potentially detrimental immune cells. However, exercise-associated apoptosis is thought to induce a temporarily decline of the adaptive immune competence in the early post-exercise period. The purpose of the present study was to investigate if the aerobic endurance training status affects the sensitivity of human peripheral blood lymphocytes towards different types of apoptosis inducers and secondly, if this is mediated by the modulation of apoptosis-associated proteins and microRNAs. Collected at resting conditions, isolated lymphocytes of endurance trained athletes (ET) and healthy untrained subjects were either exposed to phytohemagglutinin-L (PHA-L), hydrogen peroxide (H2O2), or dexamethasone (DEX) as apoptosis inducer. Results revealed no significant differences between ET and UT in terms of lymphocyte apoptosis immediately following isolation as determined by flow cytometry using annexin V staining. After 24 h of ex vivo cultivation, lymphocytes of ET showed a reduced sensitivity to PHA-L-induced lymphocyte apoptosis which was accompanied by a noticeably up-regulation of the prominent apoptosis inhibitor genes X-linked inhibitor of apoptosis (XIAP) and Cyclin dependent kinase inhibitor 1B (CDKN1B) as analyzed by quantitative real-time PCR. Moreover, a trend was observed for the suppression of the corresponding pro-apoptotic miR-221. Lymphocyte apoptosis in control, H2O2 and DEX treated cells was not affected by aerobic endurance training status. However, distinct molecular signatures could be identified in un-treated control samples characterized by a counterbalanced modulation of pro- and anti-apoptotic mediators in ET. The results of the current study suggest that lymphocytes adapt to repetitive endurance exercise training by promoting lymphocyte homeostasis and increasing their resistance to apoptosis. This could be based on an up-regulation of anti-apoptotic proteins and a reduction in pro-apoptotic microRNAs which together tightly regulate the genetically defined apoptotic pathways governed by the type of apoptosis stimuli. Thus, the lymphocytes of endurance-trained athletes may be primed to counteract the transient immune suppression post-exercise.

Effects of Traumeel (Tr14) on recovery and inflammatory immune response after repeated bouts of exercise: a double-blind RCT.

PURPOSE: The purpose of this double-blind, randomized, placebo-controlled clinical trial was to investigate the effects of the natural combination medicine Traumeel (Tr14) consisting of 14 diluted biological and mineral components on the inflammatory immune response and recovery up to 72 h after repetitive bouts of bicycle tests. METHODS: Antigen-stimulated IL-1ra and IL-6 were defined as primary outcome measures. Moreover, various immunological and serum muscle damage markers were investigated. The evaluation was performed using the score of the area under the curve with respect to increase (AUCi) for 24 and 72 h after the second exercise test (EX2). RESULTS: The Tr14 group indicated a lower decrease of lymphocytes by tendency (p = 0.06) and a lower activation of lymphocyte activation markers (CD62L absolute: p = 0.04; CD69: p = 0.01 and CD69 absolute: p = 0.05) in the period 24 h after EX2. In addition, the Tr14 group indicated a higher expression of antigen-stimulated CCL3 (p = 0.01), CCL4 (p = 0.07) and serum CCL2 (p = 0.05) in the period 24 h after EX2. There was a tendentially lower decrease of monocytes (p = 0.09) and a lower expression of antigen-stimulated MMP-3 (p = 0.01) in the Tr14 group in the period 72 h after EX2. However, antigen-stimulated IL-1ra and IL-6 showed no group differences. CONCLUSION: In line with the previous results, it was shown that Tr14 attenuates the adaptive immune response partially. Furthermore, the results indicate that Tr14 is able to stimulate the innate immune system via an increased production of pro-inflammatory chemokines. It is speculated that the higher expression of chemokines might play a role in the regeneration and recovery after exercise.

Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT.

The present double-blind, randomized, placebo-controlled clinical trial intended to test whether ingestion of a natural combination medicine (Tr14 tablets) affects serum muscle damage and inflammatory immune response after downhill running. 96 male subjects received Tr14 tablets, which consist of 14 diluted biological and mineral components, or a placebo for 72 h after the exercise test, respectively. Changes in postexercise levels of various serum muscle damage and immunological markers were investigated. The area under the curve with respect to the increase (AUCi) of perceived pain score and creatine kinase (CK) were defined as primary outcome measures. While for CK the p value of the difference between the two groups is borderline, the pain score and muscle strength were not statistically significant. However, a trend towards lower levels of muscle damage (CK, p = 0.05; LDH, p = 0.06) in the Tr14 group was shown. Less pronounced lymphopenia (p = 0.02), a trend towards a lower expression of CD69 count (p = 0.07), and antigen-stimulated ICAM-1 (p = 0.01) were found in the verum group. The Tr14 group showed a tendentially lower increase of neutrophils (p = 0.10), BDNF (p = 0.03), stem cell factor (p = 0.09), and GM-CSF (p = 0.09) to higher levels. The results of the current study indicate that Tr14 seems to limit exercise-induced muscle damage most likely via attenuation of both innate and adaptive immune responses. This study was registered with ClinicalTrials.gov (NCT01912469).

Supplementing healthy rats with a high-niacin dose has no effect on muscle fiber distribution and muscle metabolic phenotype.

PURPOSE: It was recently shown that niacin prevents the obesity-induced type I to type II fiber switching in skeletal muscle of obese rats and favors the development of a more oxidative metabolic phenotype and thereby increases whole body utilization of fatty acids. Whether niacin also causes type II to type I fiber switching in skeletal muscle of healthy rats has not been investigated yet. Thus, the present study aimed to investigate whether niacin supplementation influences fiber distribution and metabolic phenotype of different skeletal muscles with a distinct type I-to-type II fiber ratio in healthy rats. METHODS: Twenty-four male, 10-week-old Sprague-Dawley rats were randomly assigned into two groups of 12 rats each and fed either a control diet with 30 mg supplemented niacin/kg diet (control group) or a high-niacin diet with 780 mg supplemented niacin/kg diet (high-niacin group). RESULTS: After 27 days of treatment, the percentage number of type I fibers in rectus femoris, gastrocnemius, and tibialis anterior muscles was 5-10% greater in the niacin group than in the control group, but did not differ between groups in soleus and vastus intermedius muscles. Transcript levels of genes encoding transcription factors regulating fiber switching, fiber-specific myosin heavy chain isoforms, and proteins involved in fatty acid utilization, oxidative phosphorylation, and angiogenesis did not differ between groups. CONCLUSIONS: The results show that niacin has only negligible effects on fiber distribution and its regulation as well as the metabolic phenotype of skeletal muscle in healthy rats.

Acute exercises induce disorders of the gastrointestinal integrity in a murine model.

PURPOSE: Many endurance athletes complain about gastrointestinal (GI) symptoms. It is assumed that exercise-induced shift of perfusion with consecutive hypoperfusion of the enteral vascular system leads to an increased GI permeability and tissue damage. Therefore, the aim of the study was to investigate permeability, apoptosis, electrogenic ion transport (Isc), and tissue conductance (Gt) of the small intestine in a murine exercise model. METHODS: After spirometry, male Swiss CD-1 mice were subjected to an intensive treadmill exercise (80% VO2max). Sedentary mice served as controls. The small intestine was removed at several time intervals post-exercise. Apoptotic cells were determined by the TUNEL method, while fluorescein isothiocyanate dextran permeation indicated intestinal permeability. The Gt and Isc measurements were carried out in a modified Ussing chamber. RESULTS: Apoptosis of epithelial cells increased continuously until 24 h post exercise (0.8 ± 0.42 versus 39.2 ± 26.0%; p < 0.05). Compared with the control group the permeability increased 2 h after exercise (0.47 ± 0.07 versus 0.67 ± 0.14 FU/min; p < 0.05). Isc measurements of the ileum were augmented after 24 h (3.33 ± 0.56 versus 5.77 ± 1.16 µEq/h/cm(2); p < 0.05). At this time the Gt increased as well (28.8 ± 3.37 versus 32.5 ± 2.59 mS/cm(2); p < 0.05). CONCLUSION: In the murine exercise model there is evidence that after intense endurance exercise repair processes occur in small intestinal epithelial cells, which affect permeability, Gt, and Isc. The formation of lamellipodia to close the "leaky" tight junctions caused by apoptosis might be an underlying mechanism.

Supplementing obese Zucker rats with niacin induces the transition of glycolytic to oxidative skeletal muscle fibers.

In the present study, we tested the hypothesis that niacin increases the oxidative capacity of muscle by increasing the oxidative type I muscle fiber content. Twenty-four obese Zucker rats were assigned to 2 groups of 12 rats that were fed either a control diet (O group) or a diet supplemented with 750 mg/kg diet niacin (O+N group) for 4 wk. In addition, one group of lean rats (L group) was included in the experiment and fed the control diet for 4 wk. Plasma and liver concentrations of TG were markedly greater in obese groups than in the L group but markedly lower in the O+N group than in the O group (P < 0.05). Rats of the O+N group had a higher percentage of oxidative type I fibers and higher mRNA levels of genes encoding regulators of muscle fiber composition (Ppard, Ppargc1a, Ppargc1b), angiogenic factors (Vegfa, Vegfb), and genes involved in fatty acid utilization (Cpt1b, Slc25a20, Slc22a4, Slc22a5, Slc27a1) and oxidative phosphorylation (Cox4i1, Cox6a2) and a higher activity of the mitochondrial oxidative enzyme succinate dehydrogenase in muscle than rats of the O and L groups (P < 0.05). These niacin-induced changes in muscle metabolic phenotype are indicative of an increased capacity of muscle for oxidative utilization of fatty acids and are likely mediated by the upregulation of Ppard, Ppargc1a, and Ppargc1b, which are key regulators of muscle fiber composition, mitochondrial biogenesis, angiogenesis, and genes involved in fatty acid catabolism and oxidative phosphorylation. The increased utilization of fatty acids by muscle might contribute to the strong TG-lowering effect of niacin treatment.

Niacin supplementation increases the number of oxidative type I fibers in skeletal muscle of growing pigs.

BACKGROUND: A recent study showed that niacin supplementation counteracts the obesity-induced muscle fiber switching from oxidative type I to glycolytic type II and increases the number of type I fibers in skeletal muscle of obese Zucker rats. These effects were likely mediated by the induction of key regulators of fiber transition, PGC-1α and PGC-1ß, leading to muscle fiber switching and up-regulation of genes involved in mitochondrial fatty acid import and oxidation, citrate cycle, oxidative phosphorylation, mitochondrial biogenesis. The aim of the present study was to investigate whether niacin supplementation causes type II to type I muscle and changes the metabolic phenotype of skeletal muscles in growing pigs. RESULTS: 25 male, 11 wk old crossbred pigs (Danzucht x Pietrain) with an average body weight of 32.8 ± 1.3 (mean ± SD) kg were randomly allocated to two groups of 12 (control group) and 13 pigs (niacin group) which were fed either a control diet or a diet supplemented with 750 mg niacin/kg diet. After 3 wk, the percentage number of type I fibers in three different muscles (M. longissismus dorsi, M. quadriceps femoris, M. gastrocnemius) was greater in the niacin group and the percentage number of type II fibers was lower in the niacin group than in the control group (P < 0.05). The mRNA levels of PGC-1ß and genes involved in mitochondrial fatty acid catabolism (CACT, FATP1, OCTN2), citrate cycle (SDHA), oxidative phosphorylation (COX4/1, COX6A1), and thermogenesis (UCP3) in M. longissimus dorsi were greater in the niacin group than in the control group (P < 0.05). CONCLUSIONS: The study demonstrates that niacin supplementation induces type II to type I muscle fiber switching, and thereby an oxidative metabolic phenotype of skeletal muscle in pigs. Given that oxidative muscle types tend to develop dark, firm and dry pork in response to intense physical activity and/or high psychological stress levels preslaughter, a niacin-induced change in the muscle´s fiber type distribution may influence meat quality of pigs.

An ergonomic welding torch reduces physical load response and improves welding quality in novices: a pilot study.

Objectives. This crossover pilot study aimed to compare the physical load response of an ergonomically improved welding torch versus a conventional torch. Methods. Ten inexperienced volunteers performed an experimental augmented virtual welding trial at chest height (ASME code 1G) and overhead (ASME code 4G) with both welding torches in random order. Skeletal muscle load and fatigue were assessed by surface electromyography and changes in isometric peak force. The sensation of pain, perceived exertion and welding execution quality were defined as further outcome parameters. Results. The muscle load response in three out of eight muscles was lower in favour of the ergonomic welding torch, which went along with a lower sensation of pain and a higher working accuracy. Conclusions. An ergonomically improved welding torch reduces the acute physical load response and sensation of pain, which ultimately allows performing better, and might contribute to prevention of musculoskeletal diseases in the long term.

Sustained Endurance Training Leads to Metabolomic Adaptation.

Endurance training induces several adaptations in substrate metabolism, especially in relation to glycogen conservation. The study aimed to investigate differences in the metabolism of lipids, lipid-like substances, and amino acids between highly trained and untrained subjects using targeted metabolomics. Depending on their maximum relative oxygen uptake (VO2max), subjects were categorized as either endurance-trained (ET) or untrained (UT). Resting blood was taken and plasma isolated. It was screened for changes of 345 metabolites, including amino acids and biogenic amines, acylcarnitines, glycerophosphocholines (GPCs), sphingolipids, hexoses, bile acids, and polyunsaturated fatty acids (PUFAs) by using liquid chromatography coupled to tandem mass spectrometry. Acylcarnitine (C14:1, down in ET) and five GPCs (lysoPC a C18:2, up in ET; PC aa C42:0, up in ET; PC ae C38:2, up in ET; PC aa C38:5, down in ET; lysoPC a C26:0, down in ET) were differently regulated in ET compared to UT. TCDCA was down-regulated in athletes, while for three ratios of bile acids CA/CDCA, CA/(GCA+TCA), and DCA/(GDCA+TDCA) an up-regulation was found. TXB2 and 5,6-EET were down-regulated in the ET group and 18S-HEPE, a PUFA, showed higher levels in 18S-HEPE in endurance-trained subjects. For PC ae C38:2, TCDCA, and the ratio of cholic acid to chenodeoxycholic acid, an association with VO2max was found. Numerous phospholipids, acylcarnitines, glycerophosphocholines, bile acids, and PUFAs are present in varying concentrations at rest in ET. These results might represent an adaptation of lipid metabolism and account for the lowered cardiovascular risk profile of endurance athletes.

Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function.

Ca2+ is an important intracellular second messenger known to regulate several cellular functions. This research aimed to investigate the mechanisms of exercise-induced immunosuppression by measuring intracellular calcium levels, Ca2+-regulating gene expression, and agonist-evoked proliferation of murine splenic T lymphocytes. Mice were randomly assigned to the control, sedentary group (C), and three experimental groups, which performed a single bout of intensive and exhaustive treadmill exercise. Murine splenic lymphocytes were separated by density-gradient centrifugation immediately (E0), 3h (E3), and 24h after exercise (E24). Fura-2/AM was used to monitor cytoplasmic free Ca2+ concentration in living cells. The combined method of carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling and flow cytometry was used for the detection of T cell proliferation. The transcriptional level of Ca2+-regulating genes was quantified by using qPCR. Both basal intracellular Ca2+ levels and agonist (ConA, OKT3, or thapsigargin)-induced Ca2+ transients were significantly elevated at E3 group (p<0.05 vs. control). However, mitogen-induced cell proliferation was significantly decreased at E3 group (p<0.05 vs. control). In parallel, the transcriptional level of plasma membrane Ca2+-ATPases (PMCA), sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), TRPC1, and P2X7 was significantly downregulated, and the transcriptional level of IP3R2 and RyR2 was significantly upregulated in E3 (p<0.01 vs. control). In summary, this study demonstrated that acute exercise affected intracellular calcium homeostasis, most likely by enhancing transmembrane Ca2+ influx into cells and by reducing expression of Ca2+-ATPases such as PMCA and SERCA. However, altered Ca2+ signals were not transduced into an enhanced T cell proliferation suggesting other pathways to be responsible for the transient exercise-associated immunosuppression.

Exercise training reduces workload, improves physical performance, and promotes overall health in welders.

OBJECTIVES: Welders demonstrate a significant prevalence of work-related musculoskeletal disorders as indicated by high rates of illness-related absenteeism. The aim of the study was to investigate the effects of a 24-week exercise program on workload, physical performance, and overall health in welders. METHODS: Seventy-seven professional welders were assigned to either a control group (CG), an endurance training group (ETG), or a strength training group (STG). Both groups conducted a 24-week, standardized and progressive endurance or resistance exercise training program. Before (TP1) and after training (TP2) all participants performed an experimental welding task (EWT) in order to test the hypothesis that training would reduce the relative load (%MVC) of eight skeletal muscles measured by surface electromyography. Secondary outcome measures included further EWT-induced stress parameters and a series of health-related outcome measures. RESULTS: Results revealed a lower muscle load in participants of the ETG and STG for trapezius muscle at TP2 compared to T1 (P < .05 vs CG). Rate of perceived exertion and visual analogue scale were decreased, while increase of maximum EWT duration was found in participants of the ETG and STG after training (P < .05 vs CG). At T2, body fat (%) decreased and physical performance (bicycle exercise test, isometric strength of core muscles) increased in ETG and STG (P < .05). CONCLUSION: Both regular endurance and strength training represent effective strategies for reducing workload and improving physical performance of welders. The results emphasize the importance of physical fitness for welders and might motivate health professionals in steel-industry to offer access to exercise training programs.

Profiling of human lymphocytes reveals a specific network of protein kinases modulated by endurance training status.

To date, the effects of endurance exercise training on lymphocyte physiology at the kinome level are largely unknown. Therefore, the present study used a highly sensitive peptide-based kinase activity profiling approach to investigate if the basal activity of tyrosine (Tyr) and serine/threonine (Ser/Thr) kinases of human lymphocytes is affected by the aerobic endurance training status. Results revealed that the activity of various tyrosine kinases of the FGFR family and ZAP70 was increased, whereas the activity of multiple Ser/Thr kinases such as IKKα, CaMK4, PKAα, PKCα+δ (among others) was decreased in lymphocytes of endurance trained athletes (ET). Moreover, functional associations between several differentially regulated kinases in ET-derived lymphocytes were demonstrated by phylogenetic mapping and network analysis. Especially, Ser/Thr kinases of the AGC-kinase (protein kinase A, G, and C) family represent exercise-sensitive key components within the lymphocytes kinase network that may mediate the long-term effects of endurance training. Furthermore, KEGG (Kyoto Encyclopedia of Genes and Genomes) and Reactome pathway analysis indicate that Ras as well as intracellular signaling by second messengers were found to be enriched in the ET individuals. Overall, our data suggest that endurance exercise training improves the adaptive immune competence by modulating the activity of multiple protein kinases in human lymphocytes.

Acute exercise-induced irisin release in healthy adults: Associations with training status and exercise mode.

There is a growing interest in exploring irisin response to acute exercise; however, the associations of acute exercise-induced irisin release with training status and exercise mode are not fully understood. This study was primarily designed to evaluate these associations. Sixteen healthy adults (8 trained versus 8 untrained) underwent a bout of cycling at 80% of maximal oxygen uptake (VO2max) for 50 min, with blood drawn pre-, 10-, and 180-min post-exercise. Another 17 healthy adults performed 2 bouts of graded exercise (cycling and running) until exhaustion on separate days using a randomized cross-over design, with blood taken pre-, 0-, 10-, and 60-min post-exercise. Circulating irisin, creatine kinase (CK), aspartate aminotransferase (AST), and myoglobin (Mb) were measured, and their respective areas under the curves (AUCs) were calculated. Irisin increased 10-min after 50 min of cycling at 80% of VO2max, while its changes from baseline to post-exercise and the amount of exercise-induced irisin release (presented as AUC) were comparable between trained and untrained adults (all P > .05). Irisin remained elevated 10-min post-exhausting running but decreased towards baseline 10-min post-exhausting cycling. Exhausting running induced an increase in irisin release for the whole course of exercise and recovery periods, but cycling did not. Acute exercise-induced irisin changes seemed not related to changes of CK, aspartate AST, and Mb in general. In conclusion, acute exercise-induced irisin release is not associated with training status but might be affected by training mode. Future studies are required to investigate which exercise mode might be most efficient in altering irisin.

Exercise Affects T-Cell Function by Modifying Intracellular Calcium Homeostasis.

PURPOSE: The study aimed to investigate the effects of chronic moderate exercise on regulation of intracellular calcium signaling as an important link to proliferation capacity in murine splenic T lymphocytes. METHODS: Male CD1 Swiss mice were randomly assigned either to a control group (CG) or an exercise training group (EG). EG mice performed voluntary exercise for 3 months. Lymphocytes were isolated from murine spleens and intracellular calcium was determined by using Fura-2(AM) and fluorescence spectrometry. The combination of flow cytometry and carboxy-fluorescein succinimidyl ester labeling technique was used for determination of cell proliferation. The expression levels of Ca-regulating genes were determined by quantitative polymerase chain reaction (qPCR) analysis. RESULTS: Basal [Ca]i was significantly higher in mice from the EG compared with mice of the CG (P < 0.001, n = 6). Similarly, [Ca]i transients after stimulation with phytohemagglutinin, concanavalin A, and the anti-CD3 antibody induced were significantly increased in mice from the EG (P < 0.05, n = 5). However, no differences were found after stimulation with thapsigargin (P < 0.05, n = 5). CD3 T cells from EG showed higher mitogen-induced proliferation levels than from CG (P < 0.05/0.01, n = 5). The mRNA expression of cellular Ca-regulating genes, such as STIM1, Cav2.3, TRPV4, IP3R2, ORAI1, MCU, TRPM5, and TRPC1, were significantly downregulated (P < 0.05/0.01, n = 5). CONCLUSION: This study suggests that chronic moderate exercise improves intracellular Ca signaling in murine splenic lymphocytes. The enhanced availability of the second messenger Ca is followed by an improved cellular function such as cell proliferation. The downregulation of Ca homeostasis-related factor expression might be considered as a self-protective mechanism against elevated intracellular Ca signals.

The Immunomodulatory Effects of Physical Activity.

BACKGROUND: An individual's level of physical activity is one of a set of lifestyle and behavioral factors that can affect immune function and health. METHODS: The purpose of this review is to summarize the current knowledge in this research field and to review the recent developments in exercise immunology. RESULTS: Most studies show that regular exercise training increases immune competence and reduces the risk of infection compared to a sedentary lifestyle. In contrast, acute prolonged bouts of exercise and periods of intensified training are followed by a temporary increase in the risk of infection. These observations have been attributed to differential exercise-induced changes of a series of humoral and cellular immune system parameters. Furthermore, regular exercise training is a countermeasure against a persistent systemic inflammatory state which is a typical feature of cardiovascular and metabolic diseases is by lowering levels of pro-inflammatory cytokines. It is supposed that these effects are mediated by a modification of metabolic signals and innate immune regulation, the release of anti-inflammatory cytokines from muscle, the release of stress hormones, and a process known as browning of adipose tissue. CONCLUSION: The effects of physical activity on the immune system strongly depend on the mode and intensity of exercise or training. Thereby, considerable knowledge has accumulated concerning the significance of exercise as an important lifestyle factor for prevention and therapy of major chronic diseases.

Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice.

The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST) or a high fat diet (HFD) and subjected to regular endurance training (ET) or resistance training (RT). After 10 weeks body weight, glucose tolerance, fatty acids (FAs), circulating ceramides, cytokines, and immunological mediators were determined. The HFD induced a significant increase in body weight and a disturbed glucose tolerance (p < 0.05). An increase of plasma FA, ceramides, and inflammatory mediators in adipose tissue and serum was found (p < 0.05). Both endurance and resistance training decreased body weight (p < 0.05) and reduced serum ceramides (p < 0.005). While RT attenuated the increase of NLRP-3 (RT) expression in adipose tissue, ET was effective in reducing TNF-α and IL-18 expression. Furthermore, ET reduced levels of MIP-1γ, while RT decreased levels of IL-18, MIP-1γ, Timp-1, and CD40 in serum (p < 0.001), respectively. Although both exercise regimes improved glucose tolerance (p < 0.001), ET was more effective than RT. These results suggest that exercise improves HFD-induced complications possibly through a reduction of ceramides, the reduction of inflammasome activation in adipose tissues, and a systemic downregulation of inflammatory cytokines.

Apoptosis of T-Cell Subsets after Acute High-Intensity Interval Exercise.

INTRODUCTION: High-intensity interval training (HIT) exercise has gained much interest in both performance and recreational sports. This study aims to compare the effect of HIT versus continuous (CONT) exercise with regard to changes of circulating T cells and progenitor cells. METHODS: Subjects (n = 23) completed an HIT test and an isocaloric CONT test. Blood samples were collected before, immediately after, and 3 and 24 h postexercise for the assessment of low differentiated (CD3CD28CD57), highly differentiated T cells (CD3CD28CD57), regulatory T cells (Tregs) (CD4CD25CD127), hematopoietic progenitor cells (CD45CD34), and endothelial progenitor cells (CD45CD34KDR) by flow cytometry. The detection of apoptosis was performed by using labeling with annexin V. To analyze potential mechanisms affecting T cells, several hormones and metabolites were analyzed. RESULTS: Both exercise tests induced an increase of catecholamines, cortisol, and thiobarbituric acid-reactive substances (P < 0.05). CONT induced a higher increase of apoptosis in low differentiated T cells compared with the HIT (CONT: 3.66% ± 0.21% to 6.48% ± 0.29%, P < 0.05; HIT: 3.43% ± 0.31% to 4.71% ± 0.33%), whereas HIT was followed by a higher rate of apoptotic highly differentiated T cells (CONT: 21.45% ± 1.23% to 25.32% ± 1.67%; HIT: 22.45% ± 1.37% to 27.12% ± 1.76%, P < 0.05). Regarding Tregs, HIT induced a mobilization, whereas CONT induced apoptosis in these cells (P < 0.05). The mobilization of progenitor cells did not differ between the exercise protocols. CONCLUSION: These results suggest that HIT deletes mainly highly differentiated T cells known to affect immunity to control latent infections. By contrast, CONT deletes mainly low differentiated T cells and Tregs, which might affect defense against new infectious agents.

Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle.

BACKGROUND: In the present study, we tested the hypothesis that carnitine supplementation counteracts obesity-induced muscle fiber transition from type I to type II. METHODS: 24 obese Zucker rats were randomly divided into two groups of 12 rats each (obese control, obese carnitine) and 12 lean Zucker rats were selected for lean control group. A control diet was given to both control groups and a carnitine supplemented diet (3 g/kg diet) was given to obese carnitine group for 4 wk. Components of the muscle fiber transformation in skeletal muscle were examined. RESULTS: The plasma level of carnitine were lower in the obese control group compared to the lean control group and higher in the obese carnitine group than in the other groups (P < 0.05). Plasma concentrations of triglycerides and non-esterified fatty acids were increased in obese animals compared to lean animals and the obese carnitine group had lower level compared to the obese control group (P < 0.05). The obese carnitine group had an increased number of type I muscle fibers and higher mRNA levels of type I fiber-specific myosin heavy chain, regulators of muscle fiber transition and of genes involved in carnitine uptake, fatty acid transport, ß-oxidation, angiogenesis, tricarboxylic acid cycle and thermo genesis in M. rectus femoris compared to the other groups (P < 0.05). CONCLUSION: The results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes.

Niacin supplementation induces type II to type I muscle fiber transition in skeletal muscle of sheep.

BACKGROUND: It was recently shown that niacin supplementation counteracts the obesity-induced muscle fiber transition from oxidative type I to glycolytic type II and increases the number of type I fibers in skeletal muscle of obese Zucker rats. These effects were likely mediated by the induction of key regulators of fiber transition, PPARδ (encoded by PPARD), PGC-1α (encoded by PPARGC1A) and PGC-1ß (encoded by PPARGC1B), leading to type II to type I fiber transition and upregulation of genes involved in oxidative metabolism. The aim of the present study was to investigate whether niacin administration also influences fiber distribution and the metabolic phenotype of different muscles [M. longissimus dorsi (LD), M. semimembranosus (SM), M. semitendinosus (ST)] in sheep as a model for ruminants. For this purpose, 16 male, 11 wk old Rhoen sheep were randomly allocated to two groups of 8 sheep each administered either no (control group) or 1 g niacin per day (niacin group) for 4 wk. RESULTS: After 4 wk, the percentage number of type I fibers in LD, SM and ST muscles was greater in the niacin group, whereas the percentage number of type II fibers was less in niacin group than in the control group (P < 0.05). The mRNA levels of PPARGC1A, PPARGC1B, and PPARD and the relative mRNA levels of genes involved in mitochondrial fatty acid uptake (CPT1B, SLC25A20), tricarboxylic acid cycle (SDHA), mitochondrial respiratory chain (COX5A, COX6A1), and angiogenesis (VEGFA) in LD, SM and ST muscles were greater (P < 0.05) or tended to be greater (P < 0.15) in the niacin group than in the control group. CONCLUSIONS: The study shows that niacin supplementation induces muscle fiber transition from type II to type I, and thereby an oxidative metabolic phenotype of skeletal muscle in sheep as a model for ruminants. The enhanced capacity of skeletal muscle to utilize fatty acids in ruminants might be particularly useful during metabolic states in which fatty acids are excessively mobilized from adipose tissue, such as during the early lactating period in high producing cows.

Regular endurance exercise improves the diminished hepatic carnitine status in mice fed a high-fat diet.

SCOPE: Metabolic stress induced by chronic high-fat (HF) diet feeding or genetically induced diabetes impairs carnitine status. Herein, we tested the hypothesis that regular endurance exercise (EE) improves the HF diet-induced impairment of carnitine status through stimulating the expression of hepatic genes involved in carnitine synthesis and uptake. METHODS AND RESULTS: Eighteen male C57BL/6 mice were assigned to three groups: group S received a standard diet, group HF received a HF diet, and group HF+EE received an HF diet and was regularly exercised on a treadmill. After 10 wk, mice of the HF and the HF+EE groups were highly obese and insulin resistant compared with mice of the S group (p<0.05), but mice of the HF+EE group were less insulin resistant than those of the HF group (p<0.05). The HF group had lower carnitine concentrations and mRNA and protein levels of genes involved in carnitine synthesis and uptake in the liver than the S group (p<0.05), whereas these parameters did not differ between the S group and the HF+EE group. CONCLUSION: These findings indicate that regular EE reverses an HF diet-induced impairment of hepatic carnitine content by stimulating hepatic carnitine synthesis and uptake.