Improved Oxygen Consumption Research Articles

Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice.

This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher V̇O2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved V̇O2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.

ERCC6L2 Disease and Shwachman-Diamond Syndrome Exhibit Alterations in Metabolomes in Patient Fibroblasts

Introduction Metabolomics is an emerging tool to study metabolic alterations in cancers. It has also the potential to identify clinically relevant biomarkers for diagnosis, risk appraisal, and targeted drug development. In hematology, metabolic reprogramming is essential for normal regulation of hematopoiesis. Association of discrete metabolic alterations with explicit somatic mutations have also been reported in hematological malignancies. We have previously observed glutaminase (GLS) overexpression and improved oxygen consumption rate with excess glutamine in low glucose conditions in patient-derived fibroblasts in ERCC6L2 disease (unpublished). This prompted us to study metabolomic alterations in ERCC6L2 disease and Shwachman-Diamond syndrome (SDS) induced strictly by the germline ERCC6L2 and SBDS mutations. Both inherited bone marrow failure (BMF) syndromes carry considerable tendency of somatic TP53 mutagenesis predisposing patients to a high risk myeloid malignancy. Our aim here was to identify potential drug targets by targeted metabolomics. Methods We examined patient-derived skin fibroblasts (ERCC6L2 disease, n=4; SDS, n=4) and healthy controls (n=4) and performed targeted metabolomics with U-13C-D-glucose and U-13C-L-glutamine labeling. Fibroblasts were seeded on six-well plates and on the following day exposed to 13C-glucose (25mM) or 13C-glutamine (2mM) label containing medium for 30 or 120 minutes. Next, metabolites were extracted and quantified with liquid chromatography mass spectrometer. The results were normalized to total metabolite intensity per sample. Results In 13C-glucose labeled samples, we detected statistically significantly lower intensity of pyruvate M+3 in both ERCC6L2 and SDS fibroblasts compared to control at 30 minutes, which persisted at 120 minutes in SDS cells. In the TCA cycle, malate M+3 labeling indicates pyruvate carboxylase (PC) activity and M+2 labeling pyruvate dehydrogenase activity (PDH) (Figure 1). We found a significantly higher portion of malate M+3 than M+2 in SDS cells at all time points, suggesting lower PDH and higher PC activity in SDS cells. Additionally, we detected higher levels of alanine M+3 in SDS samples. As pyruvate is a source for alanine synthesis, we suspect an alteration in pyruvate metabolism; potentially to overcome challenges in pyruvate oxidation due to either decrease in the respiratory chain function or PDH activity. In 13C-glutamine labeled samples, we detected statistically significantly higher intensity of glutamine M+5 and M+4 in ERCC6L2 samples at 30 minutes compared to control and SDS cells. Glutamine is first converted to glutamate by glutaminase (GLS), after which it enters the TCA cycle as ketoglutarate (KG) (Figure 1). In addition to glutamine, we detected an increase, although not statistically significant, in glutamate M+5 and M+4, as well as KG M+5, in ERCC6L2 cells at 30 minutes. A similar trend was observed in the subsequent TCA cycle intermediates succinic acid M+4, fumarate M+4, and malate M+4. At 120 minutes, there was no difference in metabolite intensities between the groups, suggesting a potentially faster glutamine uptake by ERCC6L2 cells. Conclusions Our analysis using non-hematopoietic tissue provides understanding of metabolic weak links not confounded by somatic events occurring early in the disease course in ERCC6L2 and SDS patients. Our findings imply increased glutamine utilization in ERCC6L2 cells and altered pyruvate metabolism in SDS cells. Therefore, these metabolic pathways are attractive drug targets (summarized in Figure 1). Further studies are needed to determine their potential in supporting the compromised hematopoiesis to reduce the stress for somatic mutagenesis.

Effect of Coronary Sinus Reducer Implantation on Aerobic Exercise Capacity in Refractory Angina Patients—A CROSSROAD Study

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina pectoris. However, there is no evidence from a randomized trial that would show an improvement in exercise capacity after this treatment. The aim of this study was to evaluate the influence of CSR treatment on maximal oxygen consumption and compare it to a sham procedure. Twenty-five patients with refractory angina pectoris (Canadian Cardiovascular Society (CCS) class II–IV) were randomized to a CSR implantation (n = 13) or a sham procedure (n = 12). At baseline and after 6 months of follow-up, the patients underwent symptom-limited cardiopulmonary exercise testing with an adjusted ramp protocol and assessment of angina pectoris using the CCS scale and Seattle angina pectoris questionnaire (SAQ). In the CSR group, maximal oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min (p = 0.03) but did not change in the sham group (p = 0.53); p for intergroup comparison was 0.03. In contrast, there was no difference in the improvement of the CCS class or SAQ domains. To conclude, in patients with refractory angina and optimized medical therapy, CSR implantation may improve oxygen consumption beyond that of optimal medical therapy.

Endothelial SIRT-1 has a critical role in the maintenance of capillarization in brown adipose tissue

Brown adipose tissue (BAT) has critical roles in thermogenesis and systemic metabolism. Capillary rarefaction was reported to develop in BAT with dietary obesity, and previous studies showed that suppression of vascular endothelial growth factor A (VEGF-A) reduced capillary density in BAT, promoting the functional decline of this organ. Capillarization is regulated through the balance between angiogenesis and vasculogenesis on the one hand and apoptosis of endothelial cells (ECs) on the other; however, the role of EC apoptosis in BAT remained to be explored. In studies testing the role of boysenberry polyphenols (BoyP) in BAT, we found that BoyP decreased EC apoptosis, enhanced capillarization in BAT, and ameliorated dietary BAT dysfunction, which was associated with the upregulation of nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin 1 (SIRT-1) in ECs. Our studies suggest that EC SIRT-1 would be one of the potential targets of BoyP that contributes to BAT capillarization and function.

Baleen whale inhalation variability revealed using animal-borne video tags.

Empirical metabolic rate and oxygen consumption estimates for free-ranging whales have been limited to counting respiratory events at the surface. Because these observations were limited and generally viewed from afar, variability in respiratory properties was unknown and oxygen consumption estimates assumed constant breath-to-breath tidal volume and oxygen uptake. However, evidence suggests that cetaceans in human care vary tidal volume and breathing frequency to meet aerobic demand, which would significantly impact energetic estimates if the findings held in free-ranging species. In this study, we used suction cup-attached video tags positioned posterior to the nares of two humpback whales (Megaptera novaeangliae) and four Antarctic minke whales (Balaenoptera bonaerensis) to measure inhalation duration, relative nares expansion, and maximum nares expansion. Inhalation duration and nares expansion varied between and within initial, middle, and terminal breaths of surface sequences between dives. The initial and middle breaths exhibited the least variability and had the shortest durations and smallest nares expansions. In contrast, terminal breaths were highly variable, with the longest inhalation durations and the largest nares expansions. Our results demonstrate breath-to-breath variability in duration and nares expansion, suggesting differential oxygen exchange in each breath during the surface interval. With future validation, inhalation duration or nares area could be used alongside respiratory frequency to improve oxygen consumption estimates by accounting for breath-to-breath variation in wild whales.

Polyprenol Liposomes Improve the Efficiency of Oxygen Usage in Well-Trained Amateur Athletes

Abstract Polyprenols are natural substances that are known for their role as cell membrane protectors from peroxidation. However, there is a lack of information about their effect on the performance of athletes. Therefore, we studied the effects of polyprenol on athlete performance. A total of 30 male floorball players participated in this study, 16 of whom were taking 30 mg polyprenol liposome caps and 14 of whom were not. All of the participants underwent VO2max exhaustive incremental cycling testing, before and after the use of polyprenols. VO2peak and other cardiorespiratory variables were measured to evaluate cardiorespiratory adaptation. For the polyprenol users (PU) the oxygen pulse (O2/HR) increased by 0.9 ml/beat, while in the control group (C) decreased by 0.4 ml/beat from before to after the use of polyprenols (p &lt; 0.05). The diastolic pressure (Pdia) decreased by 4 mmHg for the PU, while it increased by 10 mmHg in the C (p &lt; 0.05). The stroke volume (SVc) in the PU increased by 2.9 ml, while that in the C decreased by 7.4 ml (p &lt; 0.05). In conclusion, polyprenols improved oxygen consumption efficiency by increasing SVc and O2/HR.

Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C.

Cardiorenal syndrome (CRS) is a pathological link between the kidneys and heart, in which an insult in a kidney or heart leads the other organ to incur damage. CRS is classified into five subtypes, and type 3 (CRS3) is characterized by acute kidney injury as a precursor to subsequent cardiovascular changes. Mitochondrial dysfunction and oxidative and nitrosative stress have been reported in the pathophysiology of CRS3. It is known that vitamin C, an antioxidant, has proven protective capacity for cardiac, renal, and vascular endothelial tissues. Therefore, the present study aimed to assess whether vitamin C provides protection to heart and the kidneys in an in vivo CRS3 model. The unilateral renal ischemia and reperfusion (IR) protocol was performed for 60 min in the left kidney of adult mice, with and without vitamin C treatment, immediately after IR or 15 days after IR. Kidneys and hearts were subsequently collected, and the following analyses were conducted: renal morphometric evaluation, serum urea and creatinine levels, high-resolution respirometry, amperometry technique for NO measurement, gene expression of mitochondrial dynamic markers, and NOS. The analyses showed that the left kidney weight was reduced, urea and creatinine levels were increased, mitochondrial oxygen consumption was reduced, NO levels were elevated, and Mfn2 expression was reduced after 15 days of IR compared to the sham group. Oxygen consumption and NO levels in the heart were also reduced. The treatment with vitamin C preserved the left kidney weight, restored renal function, reduced NO levels, decreased iNOS expression, elevated constitutive NOS isoforms, and improved oxygen consumption. In the heart, oxygen consumption and NO levels were improved after vitamin C treatment, whereas the three NOS isoforms were overexpressed. These data indicate that vitamin C provides protection to the kidneys and some beneficial effects to the heart after IR, indicating it may be a preventive approach against cardiorenal insults.

Complex II subunit SDHD is critical for cell growth and metabolism, which can be partially restored with a synthetic ubiquinone analog

BackgroundSuccinate dehydrogenase (Complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate in the mitochondrial Krebs cycle and transferring electrons from succinate to ubiquinone in the mitochondrial electron transport chain (ETC). Mutations in Complex II are associated with a number of pathologies. SDHD, one of the four subunits of Complex II, serves by anchoring the complex to the inner-membrane and transferring electrons from the complex to ubiquinone. Thus, modeling SDHD dysfunction could be a valuable tool for understanding its importance in metabolism and developing novel therapeutics, however no suitable models exist.ResultsVia CRISPR/Cas9, we mutated SDHD in HEK293 cells and investigated the in vitro role of SDHD in metabolism. Compared to the parent HEK293, the knockout mutant HEK293ΔSDHD produced significantly less number of cells in culture. The mutant cells predictably had suppressed Complex II-mediated mitochondrial respiration, but also Complex I-mediated respiration. SDHD mutation also adversely affected glycolytic capacity and ATP synthesis. Mutant cells were more apoptotic and susceptible to necrosis. Treatment with the mitochondrial therapeutic idebenone partially improved oxygen consumption and growth of mutant cells.ConclusionsOverall, our results suggest that SDHD is vital for growth and metabolism of mammalian cells, and that respiratory and growth defects can be partially restored with treatment of a ubiquinone analog. This is the first report to use CRISPR/Cas9 approach to construct a knockout SDHD cell line and evaluate the efficacy of an established mitochondrial therapeutic candidate to improve bioenergetic capacity.

One Bout of Aerobic Exercise Elicits Alterations in The Expression of Mitochondrial Unfolded Protein Response (UPRmt) Markers in Skeletal Muscle

Muscle contractions during aerobic exercise stimulate molecular pathways to promote the production of new mitochondria, and improve their function. These adaptations translate into improved oxygen consumption and metabolic capacity of skeletal muscle. However, the increased drive for mitochondrial biogenesis during contractile activity causes an accumulation of misfolded proteins, disrupting mitochondrial homeostasis. The action of the UPRmt, a cytoprotective stress response pathway, is required to mitigate the associated proteotoxicity. This protein quality control mechanism favours the transcription of mitochondrial chaperones and proteases to refold and degrade the defective proteins, while inhibiting global protein translation. However, the regulation and activity of the UPRmt in helping skeletal muscle adapt to exercise stress during and after an acute bout of exercise has yet to be determined. Thus, to investigate this, mice were separated into sedentary (SED), acute exercise (AE) and acute exercise with recovery (AER) groups (n=4/group). The exercise consisted of 90-minutes of treadmill running at 15m/min. Tibialis anterior muscles were extracted from the AE groups immediately following exercise and from the AER group 3 hours post-exercise. Total RNA was isolated and mRNA levels were measured using qPCR. In line with previous data, PGC-1α mRNA increased by 50% in the AE group and increased further to 3.4-fold in the AER group. Activating transcription factor 5 (ATF5), an important regulator of UPRmt gene expression, did not change with acute exercise or recovery. ATF4, another transcription factor for stress-responsive genes, was also unchanged at the end of exercise, but was upregulated by 28% in the recovery period. mRNA levels of downstream targets of ATF5, Lon protease (LonP) and chaperones (HSP60 and GRP75) were upregulated by 18%, 24% and 77%, respectively. HSP60 mRNA returned to control levels during recovery, while GRP75 and LonP mRNAs remained elevated in the AER group. Our data indicate that acute exercise influences the expression of genes involved in both mitochondrial biogenesis and those of the UPRmt, contributing to the maintenance of organelle proteostasis in exercised muscle. Investigating the regulatory mechanisms governing this acute mitochondrial stress response is critical, as preservation of cellular function in the face of exercise-induced stress is essential for metabolic adaptations in muscle and thus, for whole-body homeostasis.

Ubiquinol (reduced coenzyme Q10) as a metabolic resuscitator in post-cardiac arrest: A randomized, double-blind, placebo-controlled trial

IntroductionUbiquinol (reduced coenzyme Q10) is essential for adequate aerobic metabolism. The objective of this trial was to determine whether ubiquinol administration in patients resuscitated from cardiac arrest could increase physiological coenzyme Q10 levels, improve oxygen consumption, and reduce neurological biomarkers of injury. Materials and methodsThis was a randomized, double-blind, placebo-controlled trial in patients successfully resuscitated from cardiac arrest. Patients were randomized to receive enteral ubiquinol (300 mg) or placebo every 12 h for up to 7 days. The primary endpoint was total coenzyme Q10 plasma levels at 24 h after enrollment. Secondary endpoints included neuron specific enolase, S100B, lactate, cellular and global oxygen consumption, neurological status, and in-hospital mortality. ResultsForty-three patients were included in the modified intention-to-treat analysis. Median coenzyme Q10 levels were significantly higher in the ubiquinol group as compared to the placebo group at 24 h (441 [IQR, 215–510] ηg/mL vs. 113 [IQR, 94–208] ηg/mL, P < 0.001). Similar results were observed at 48 and 72 h. There were no differences between the two groups in any of the secondary endpoints. Median neuron specific enolase levels were not different between the two groups at 24 h (16.8 [IQR, 9.5–19.8] ηg/mL vs. 8.2 [IQR, 4.3–19.1] ηg/mL, P = 0.61). ConclusionsAdministration of enteral ubiquinol increased plasma coenzyme Q10 levels in post-cardiac arrest patients as compared to placebo. There were no differences in neurological biomarkers and oxygen consumption between the two groups.

Abilities of physical rehabilitation in pneumonia

The use of physical rehabilitation methods, in particular respiratory rehabilitation for pneumonia, allows to increase the tolerance to physical activity, improve oxygen consumption and endurance of patients compared to the initial level, reduce the frequency and duration of their hospitalization, as well as significantly improve the effectiveness of drug therapy. In the first stage of assisting patients with pneumonia of various genesis, therapeutic exercises are recommended that improve drainage function of the bronchi and promotes the discharge of bronchial mucous. Prescription of physiotherapeutic methods of treatment, which have a bactericidal, anti-inflammatory, anti-edema and resorption effects, significantly increase the effectiveness of complex therapeutic measures. A comprehensive approach to the treatment of pneumonia can produce better results by using all therapeutic physical exercise and physiotherapy options that have proven effective over many decades.

Effects of upper extremity aerobic exercise training on oxygen consumption, exercise capacity, dyspnea and quality of life in patients with pulmonary arterial hypertension

BackgroundPulmonary and extrapulmonary impairments are prevalent in pulmonary arterial hypertension (PAH) which is a rare, chronic and progressive disease. ObjectivesTo investigate the effects of upper extremity aerobic exercise training on exercise capacity, oxygen consumption, dyspnea and quality of life in patients with PAH. MethodsIn a prospective, randomized controlled, double-blinded study, eleven patients in training group applied upper extremity aerobic exercise training (50–80% of maximal heart rate), 15–45 min/day, 3 days a week for 6 weeks and 11 patients in control group alternating active upper extremity exercises for the same period. Exercise capacity evaluated using six minute walk test (6MWT), oxygen consumption simultaneously measured during 6MWT using a portable instrument, dyspnea modified Borg scale and Modified Medical Research Council dyspnea scale and quality of life Short Form 36 Health Survey, before and after the exercise training. ResultsBaseline characteristics of groups were similar (p>0.05). Dyspnea (p<0.001) and peak oxygen consumption (p = 0.031) were significantly improved in training group compared the controls. Dyspnea, exercise capacity, peak oxygen consumption, minute ventilation, tidal volume, end tidal carbon-dioxide pressure, and vitality, social functioning and role-physical were significantly improved within training group (p<0.05). Oxygen consumption at anaerobic threshold were significantly decreased within control group (p<0.05). ConclusionsUpper extremity aerobic exercise training improves oxygen consumption, and decreases dyspnea perception. It is a safe and effective intervention in patients with PAH. (ClinicalTrials.gov registration: NCT02371733).

Melatonin Inhibits Formation of Mitochondrial Permeability Transition Pores and Improves Oxidative Phosphorylation of Frozen-Thawed Ram Sperm.

Structural and functional damages to mitochondria of frozen-thawed sperm are a typical cryoinjury, with mitochondrial permeability transition pore (MPTP) formation being the hallmark change. Mitochondria are both a primary synthesis site and principle target for melatonin; this compound can directly inhibit MPTP formation and therefore confer protection at a mitochondrial level. The objective was to determine effects of melatonin on MPTP opening, viability, motility, and oxidative phosphorylation (OXPHOS) of frozen-thawed ram sperm. Ram semen was diluted in glucose-egg yolk buffer with 0 or 10−7 M melatonin (frozen and frozen + melatonin groups, respectively) and slow frozen, with fresh semen as Control. In frozen-thawed sperm, melatonin inhibited MPTP opening and lactate concentrations and improved sperm viability, motility, acetyl-CoA concentration and adenosine triphosphate (ATP) production. With regard to the underlying physiological mechanism, melatonin suppressed movement of citrate synthase, isocitrate dehydrogenase, oxoglutarate dehydrogenase complex, and F0F1-ATP synthase permeability from mitochondrial to cytosolic fractions induced by MPTP opening; furthermore, it increased mRNA expressions of respiratory chain complex components and activities of complexes I, II, III, and IV and thereby improved oxygen consumption capacity in frozen-thawed sperm. In conclusion, melatonin improved OXPHOS of frozen-thawed ram sperm, attributed to inhibition of cryopreservation-induced MPTP opening.

The effects of respiratory muscle resistance training on lactate threshold: a potential effort to prevent muscle fatigue during exercise

Respiratory muscle resistance training (RMRT) is the practice of breathing through a respiratory mouth-device designed to restrict airflow to the user, increase airway resistance and subsequently increase the work necessary for the respiratory muscles to inspire and expire. During periods of exercise, there is an elevation in blood lactate levels as well as H+, which is a major contributing factor to exercise fatigue. The resultant elevated plasma acidity is compensated by an increased ventilation rate, which leads to increased expiration and removal of carbon dioxide (CO2) from the body. It was hypothesized that healthy college students that undergo four weeks of RMRT exercise will have improved oxygen consumption at the point of lactate threshold (VO2LT) during a graded exercise running test. The experimental group used an Expand-a-Lung RMRT device 5 times a week and tested weekly for four weeks by using near-infrared spectroscopy (NIRS) with a BSX Insight blood oxygenation sensor to measure the amount of oxygen-saturated hemoglobin (%SmO2) in the calf muscle. Our preliminary results show some improvement in ventilation in the experimental group, with tidal volume significantly increasing the most. The VO2 at lactate threshold did show an increase, providing support for our original hypothesis.

Insulin Protects Cortical Neurons Against Glutamate Excitotoxicity.

Glutamate excitotoxicity is implicated in the pathogenesis of numerous diseases, such as stroke, traumatic brain injury, and Alzheimer’s disease, for which insulin resistance is a concomitant condition, and intranasal insulin treatment is believed to be a promising therapy. Excitotoxicity is initiated primarily by the sustained stimulation of ionotropic glutamate receptors and leads to a rise in intracellular Ca2+ ([Ca2+]i), followed by a cascade of intracellular events, such as delayed calcium deregulation (DCD), mitochondrial depolarization, adenosine triphosphate (ATP) depletion that collectively end in cell death. Therefore, cross-talk between insulin and glutamate signaling in excitotoxicity is of particular interest for research. In the present study, we investigated the effects of short-term insulin exposure on the dynamics of [Ca2+]i and mitochondrial potential in cultured rat cortical neurons during glutamate excitotoxicity. We found that insulin ameliorated the glutamate-evoked rise of [Ca2+]i and prevented the onset of DCD, the postulated point-of-no-return in excitotoxicity. Additionally, insulin significantly improved the glutamate-induced drop in mitochondrial potential, ATP depletion, and depletion of brain-derived neurotrophic factor (BDNF), which is a critical neuroprotector in excitotoxicity. Also, insulin improved oxygen consumption rates, maximal respiration, and spare respiratory capacity in neurons exposed to glutamate, as well as the viability of cells in the MTT assay. In conclusion, the short-term insulin exposure in our experiments was evidently a protective treatment against excitotoxicity, in a sharp contrast to chronic insulin exposure causal to neuronal insulin resistance, the adverse factor in excitotoxicity.

Enhancing the erythritol production by Yarrowia lipolytica from waste oil using loofah sponge as oil-in-water dispersant

Waste oil is an economical alternative carbon resource in Yarrowia-based erythritol production, but the water insolubility limits its further utilization. Loofah sponge (LS), a natural polymer material and accessible agricultural waste, was selected as oil-in-water dispersant in this study. In the oil–erythritol cultivation system with LS addition, efficient oil dispersion and enhanced erythritol production (by ˜30%) were achieved, with high biomass and scarce residual oil in the medium. Up to 60.0 g/L of waste oil could be completely consumed under the effect of LS, resulting to an erythritol yield of 0.76 ± 0.03 g/g oil. Scanning electron microscopy (SEM) images and reusability experiments showed that the LS fiber was well preserved and could be stable for more than five continuous cycles in this process. The changes in activities of the metabolic enzymes suggested an enhanced carbon flux in erythritol synthesis pathway, which was accompanied with an improved oxygen consumption. Moreover, with LS addition, scale-up and fed-batch cultivations was well conducted, up to 114.3 ± 1.8 g/L of erythritol was produced from waste oil when the two cultivation strategies were combined. This study demonstrated an efficient and eco-friendly method for the utilization of waste oily substrates in production of microbial metabolites.

Low- and high-intensity one-week occlusion training improves muscle oxygen consumption and reduces muscle fatigue.

Low-intensity resistance exercises with blood flow restriction have been shown is effective to increase muscular strength and hypertrophy. However, the effects of combined training: one-week occlusion training with various exercise intensities by using less occlusion pressure on muscle strength improvement, fatigability and their work capacity are not clear. Participants (N.=24) were middle-distance runners with 4-6 years of training experience. A control group without blood flow restriction (N.=12, age 23±1 years) and an experimental group with blood flow restriction (N.=12, age 22±1 years). In this study, the calf muscles were impacted by the training with occlusion 120 mmHg. We used intensive one-week daily training, whereby exercise intensity was gradually increased daily from 20% to 80% of maximal voluntary contraction (MVC) and then decreased to 60% by the end of the week. MVC of foot flexion muscles after the one-week occlusion training in the experimental group and control group increased (P<0.05) by 5.6±1.3% and 5.3±1.2%, respectively. Meanwhile in experimental group work capacity improved only 2.4±3.5% (P>0.05) and in control group it significantly decreased 11.8±2.5% (P<0.05). StO2 decreased during exercise test from the baseline 100% to 45.2±4.3% before occlusion training and to 34.6±6.2% after the week of occlusion training (P<0.05). Intensive one-week training with occlusion with varying intensity improves resistance to fatigue and recovery after training. This kind of training improves oxygen consumption while exercising.

Salivary nitrate-nitrite conversion capacity after nitrate ingestion and incidence of Veillonella spp. in elderly individuals.

Dietary nitrate has several beneficial effects, including blood pressure reduction and improved oxygen consumption efficiency, but in order to do so it must first be reduced to nitrite by oral bacteria. Veillonella spp., a strictly anaerobic group, are the most prevalent nitrate-reducing bacteria in the oral cavity. In response to some early studies that have hinted at inter- and intra-individual variation in salivary nitrate-nitrite conversion capacity, the purpose of the present study was to investigate the incidence of and variation in the Veillonella species V. atypica, V. dispar, and V. rogosae by direct PCR and to assess salivary nitrate-nitrite conversion capacity and its reproducibility after dietary nitrate consumption in 24 elderly individuals. V. atypica, V. dispar, and V. rogosae were detected in 10 (41.7%), 24 (100%), and 14 (58.3%) participants, respectively. The coefficients of correlation between the first and second experiments on increased nitrate/nitrite were 0.637 and 0.583, respectively, both of which were statistically significant (P < 0.01). In both experiments, 6 participants produced relatively low levels of nitrite (<0.5 mM Δ nitrite) while 7 produced relatively high levels (>1.0 mM Δ nitrite). The data suggested that V. dispar was the most prevalent species, being present even in individuals producing low levels of salivary nitrite.

Attenuation of obesity and insulin resistance by fish oil supplementation is associated with improved skeletal muscle mitochondrial function in mice fed a high-fat diet

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to improve insulin sensitivity and glucose homeostasis in animal models of insulin resistance, but the involved mechanisms still remain unresolved. In this study, we evaluated the effects of fish oil (FO), a source of n-3 PUFAs, on obesity, insulin resistance and muscle mitochondrial function in mice fed a high-fat diet (HFD). C57Bl/6 male mice, 8 weeks old, were divided into four groups: control diet (C), high-fat diet (H), C+FO (CFO) and H+FO (HFO). FO was administered by oral gavage (2 g/kg b.w.), three times a week, starting 4 weeks before diet administration until the end of the experimental protocol. HFD-induced obesity and insulin resistance associated with impaired skeletal muscle mitochondrial function, as indicated by decreased oxygen consumption, tricarboxylic acid cycle intermediate (TCAi) contents (citrate, α-ketoglutarate, malate and oxaloacetate), oxidative phosphorylation protein content and mitochondrial biogenesis. These effects were associated with elevated reactive oxygen species production, decreased PGC1-a transcription and reduced Akt phosphorylation. The changes induced by the HFD were partially attenuated by FO, which decreased obesity and insulin resistance and increased mitochondrial function. In the H group, FO supplementation also improved oxygen consumption; increased TCAi content, and Akt and AMPK phosphorylation; and up-regulated mRNA expression of Gpat1, Pepck, catalase and mitochondrial proteins (Pgc1α, Pparα, Cpt1 and Ucp3). These results suggest that dietary FO attenuates the deleterious effects of the HFD (obesity and insulin resistance) by improving skeletal muscle mitochondrial function.

Emerging Role of the Mitochondrial Outer Membrane Translocator Protein (TSPO) in Heart Failure and Mitochondrai Quality Control

Introduction: Mitochondrial dysfunction is a hallmark of heart failure (HF), resulting in decreased energy production and impaired mitochondrial quality control (mitophagy) with resultant contractile dysfunction and cell death. The 18-kDa mitochondrial translocator protein (TSPO) has been considered a part of the mitochondrial permeability transition pore (mPTP) for a long time; however, its role in mPTP regulation is now debatable and the precise role of the TSPO in cardiac physiology and HF remains poorly understood.Objective: Determine the role of TSPO in a murine pressure-overload model of HF.Methods and Results: Conditional, cardiac-specific TSPO knockout (KO) mice were generated using the Cre-loxP system. Pressure overload by transverse aortic constriction (TAC) for 8 weeks significantly increased TSPO expression in wild type (WT) mice, but not in KO mice. While WT TAC mice showed a marked reduction in systolic function, KO TAC mice did not have a significant reduction in ejection fraction, and also exhibited fewer clinical HF signs (less cardiac dilation and fibrosis). TAC reduced mitochondrial calcium uptake and enhanced mPTP opening in permeabilized myocytes from WT animals. Calcium uptake was restored in TAC KO mice without significant effect on mPTP activity. The restoration of the mitochondrial calcium uptake coincided with reduced oxidative stress, improved oxygen consumption rate, and enhanced ATP generation and mitochondrial reserve capacity. In WT TAC, elevated mitochondrial accumulation of mCherry-Parkin1 was not coupled to the increase in LC3-autophagosomes formation indicating impaired mitophagy. In contrast, mitophagy was normalized in TSPO KO.Conclusions: These data suggest a novel mechanism to prevent HF at the cellular level via normalization of TSPO levels which leads to preservation of mitochondrial calcium uptake, oxidative phosphorylation, and mitochondrial mt-QC resulting in preservation of mitochondrial integrity and cell survival.