Improved Energy Metabolism Research Articles

Effect of dietary supplementation of Lactobacillus acidophilus on blood biochemical profile, antioxidant activity and plasma immunoglobulin level in neonatal Murrah buffalo calves

An experiment was designed to evaluate the effect of dietary supplementation of Lactobacillus acidophilus on blood biochemical profile, antioxidant activity and plasma immunoglobulin level in neonatal Murrah buffalo calves. The 90 day trial was conducted on 24 neonatal Murrah buffalo calves randomly divided into 4 dietary treatments, viz. CON (basal diet alone), T1 (basal diet + L. acidophilus as a fermented milk @ 100 mL/calf/day having 108 CFU/mL), T2 (basal diet + L. acidophilus as a fermented milk @ 200 mL/calf/day having 108 CFU/ml) and T3 (basal diet + L. acidophilus as a fermented milk @ 300 ml/calf/day having 108 CFU/mL). Supplementation of probiotics improved the plasma glucose level in T2 and T3 as compared to CON. Total protein (TP), plasma albumin (A), plasma globulin (G) and A:G ratio did not change with the supplementation of probiotic in calves. Total cholesterol and HDL cholesterol levels in plasma remained same in all the 4 groups. Total antioxidant (TA) activity was higher in T2 and T3 as compared to CON, whereas it was intermediate in T1. Super oxide dismutase (SOD) activity was significantly higher in T1, T2 and T3 groups as compared to CON whereas catalase and glutathione peroxidase (GPx) activity remained same in all groups throughout experimental period. The total plasma immunoglobulin and plasma IgG remained uninfluenced in all the groups. In conclusion, supplementation of L. acidophilus improved energy metabolism and antioxidant capacity in neonatal Murrah buffalo calves.

Twelve weeks of exenatide treatment increases [18F]fluorodeoxyglucose uptake by brown adipose tissue without affecting oxidative resting energy expenditure in nondiabetic males

Aims/hypothesisBrown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, possibly involving BAT activation. Interestingly, people from South Asian descent are prone to develop cardiometabolic disease. We studied the effect of GLP-1R agonism on BAT in humans, specifically in South Asians and Europids without obesity or type 2 diabetes. MethodsTwelve Dutch South Asian and 12 age- and BMI-matched Europid nondiabetic men received 12 weeks extended-release exenatide (Bydureon) in this single-arm prospective study. Before and after treatment, BAT was visualized by a cold-induced [18F]FDG-PET/CT scan and a thermoneutral MRI scan, and resting energy expenditure (REE), substrate oxidation, body composition and fasting plasma glucose and serum lipids were determined. Appetite was rated using a visual analogue scale. ResultsSince the effect of exenatide on metabolic parameters did not evidently differ between ethnicities, data of all participants were pooled. Exenatide decreased body weight (−1.5 ± 0.4 kg, p < 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered triglycerides (−15%, p < 0.05) and total cholesterol (−5%, p < 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p < 0.05) and mean standardized uptake value (+11%, p < 0.05) ([18F]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI). Conclusions/interpretationWe show for the first time that GLP-1R agonism increases [18F]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. Trial registryClinicaltrials.gov NCT03002675.

Kaempferol Treatment after Traumatic Brain Injury during Early Development Mitigates Brain Parenchymal Microstructure and Neural Functional Connectivity Deterioration at Adolescence.

Targeting mitochondrial ion homeostasis using Kaempferol, a mitochondrial Ca2+ uniporter channel activator, improves energy metabolism and behavior soon after a traumatic brain injury (TBI) in developing rats. Because of broad TBI pathophysiology and brain mitochondrial heterogeneity, Kaempferol-mediated early-stage behavioral and brain metabolic benefits may accrue from diverse sources within the brain. We hypothesized that Kaempferol influences TBI outcome by differentially impacting the neural, vascular, and synaptic/axonal compartments. After TBI at early development (P31), functional magnetic resonance imaging and diffusion tensor imaging (DTI) were applied to determine imaging outcomes at adolescence (2 months post-injury). Vehicle and Kaempferol treatments were made at 1, 24, and 48 h post-TBI, and their effects were assessed at adolescence. A significant increase in neural connectivity was observed after Kaempferol treatment as assessed by the spatial extent and strength of the somatosensory cortical and hippocampal resting-state functional connectivity (RSFC) networks. However, no significant RSFC changes were observed in the thalamus. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient, representing synaptic/axonal and microstructural integrity, showed significant improvements after Kaempferol treatment, with highest changes in the frontal and parietal cortices and hippocampus. Kaempferol treatment also increased corpus callosal FA, indicating measurable improvement in the interhemispheric structural connectivity. TBI prognosis was significantly altered at adolescence by early Kaempferol treatment, with improved neural connectivity, neurovascular coupling, and parenchymal microstructure in select brain regions. However, Kaempferol failed to improve vasomotive function across the whole brain, as measured by cerebrovascular reactivity. The differential effects of Kaempferol treatment on various brain functional compartments support diverse cellular-level mitochondrial functional outcomes in vivo.

β-Sitosterol regulated microRNAs in endothelial cells against an oxidized low-density lipoprotein.

β-Sitosterol is a natural compound widely found in many vegetable oils, nuts, and plant medicines; it lowers the cholesterol levels, enhances the production of plasminogen activators, and exhibits anticancer and antiatherogenic effects. However, the direct endothelial protection of β-sitosterol against an oxidized low-density lipoprotein (ox-LDL) is not well understood. In the present study, β-sitosterol significantly inhibited cell apoptosis (P < 0.01), increased cell migration (P < 0.01), improved energy metabolism (P < 0.05) and improved morphology after ox-LDL (50 μg ml-1) exposure following β-sitosterol (2 μg mL-1) treatment in human aortic endothelial cells (HAECs ). A total of 691 differentially expressed (DE) mRNAs were identified (579 were upregulated and 112 were downregulated, fold change ≥2.0, P < 0.05) after 24 h of β-sitosterol administration in transcriptome sequencing (β-sitosterol vs. ox-LDL), which suggested that β-sitosterol reversed 62.32% change in mRNAs induced by ox-LDL. DE mRNAs are enriched mainly in focal adhesion, ribosomes, eukaryotic translation elongation, etc. Considering that one of the enrichment is 3'-UTR-mediated translational regulation, we explored DE microRNA (miRNA). The miRNA-seq data proposed 87 up-regulated and 58 down-regulated miRNAs (fold change ≥2.0, P < 0.05) in miRNA-seq (β-sitosterol vs. ox-LDL), suggesting that β-sitosterol reversed 76.67% change in miRNAs induced by ox-LDL. The DE miRNA-DE mRNA coexpression network focused on ribosomes, cell cycle, oxidative phosphorylation, PI3K-Akt signaling pathway, TNF signaling pathway, ErbB signaling pathway, and mTOR signaling pathway. Consequently, miRNAs might be the targets of β-sitosterol and play vital roles in transcriptional regulation in endothelial protective and antiatherogenic effects against ox-LDL.

Euterpe Oleracea Mart. (Açaí) Reduces Oxidative Stress and Improves Energetic Metabolism in Myocardial Ischemia-Reperfusion Injury in Rats.

BackgroundEuterpe oleracea Mart. (açaí) is a fruit with high antioxidant capacity and could be an adjuvant strategy to attenuate ischemia-reperfusion injury.ObjectiveTo evaluate the influence of açaí in global ischemia-reperfusion model in rats.MethodsWistar rats were assigned to 2 groups: Control (C: receiving standard chow; n = 9) and Açaí (A: receiving standard chow supplemented with 5% açaí; n = 10). After six weeks, the animals were subjected to the global ischemia-reperfusion protocol and an isolated heart study to evaluate left ventricular function. Level of significance adopted: 5%.ResultsThere was no difference between the groups in initial body weight, final body weight and daily feed intake. Group A presented lower lipid hydroperoxide myocardial concentration and higher catalase activity, superoxide dismutase and glutathione peroxidase than group C. We also observed increased myocardial activity of b-hydroxyacyl coenzyme-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase in the A group as well as lower activity of the lactate dehydrogenase and phosphofructokinase enzymes. The systolic function was similar between the groups, and the A group presented poorer diastolic function than the C group. We did not observe any difference between the groups in relation to myocardial infarction area, total and phosphorylated NF-kB, total and acetylated FOXO1, SIRT1 and Nrf-2 protein expression.Conclusiondespite improving energy metabolism and attenuating oxidative stress, açai supplementation did not decrease the infarcted area or improve left ventricular function in the global ischemia-reperfusion model.

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation.

Objective To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase-associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR. Methods Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) (n = 6), control (n = 12), and SFI (n = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program-controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening. Results After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant (P < 0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group (P < 0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase-3 protein expression. Conclusion SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.

Upregulation of neuronal PGC-1α ameliorates cognitive impairment induced by chronic cerebral hypoperfusion.

Rationale: Mitochondrial dysfunction and oxidative stress occur in vascular dementia (VaD), but the specific molecular mechanism regulating these events remains unclear. Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a master regulator for mitochondrial function. This study aims to investigate whether PGC-1α is involved in the pathophysiology of VaD.Methods: We firstly generated PGC-1αf/f Eno2-Cre mice to induce neuron-specific overexpression of PGC-1α by crossbreeding PGC-1αf/f mice with Eno2-cre mice. Then, the mice were subjected to bilateral common carotid artery stenosis to induce chronic cerebral hypoperfusion. Neurological function and hippocampal PGC-1α expression was evaluated. Next, RNA-Seq analysis and Seahorse assay were performed on the hippocampal neurons. In addition, mitochondrial antioxidants, uncoupling proteins, ROS production and the activation of glial cells were also measured.Results: Our results showed that hippocampal PGC-1α expression is down-regulated in the mouse VaD model induced by chronic cerebral hypoperfusion. In contrast, neuronal PGC-1α overexpression significantly ameliorated cognitive deficits. RNA-Seq analysis indicated that PGC-1α improved energy metabolism of neurons under hypoxic condition, and Seahorse assay confirmed that PGC-1α increases the metabolic activity of neurons. Further study demonstrated that PGC-1α boosted the expressions of mitochondrial antioxidants and uncoupling proteins (UCPs), including SOD2, Prx3, GPx1, UCP2, UCP4 and UCP5, which in turn reduced reactive oxygen species (ROS) production. Moreover, the activation of microglia and astrocytes was also found to decrease in the hippocampus. All of these changes greatly contributed to protect hippocampal neurons against ischemic insults.Conclusions: PGC-1α could suppress the excessive ROS and neuroinflammation in the hippocampus, opening up a potential therapeutic target for cognitive impairment.

Multipattern botulinum toxin therapy of post-comatose long-term consciousness disorders: central effects

The data of electroencephalography, evoked potentials of the brain and positron emission tomography are analyzed before and 3 weeks after the multipattern botulinum toxin therapy of spasticity in 25 patients with post-comatose long-term consciousness disorders, including one patient who died against the backdrop gradual improvement of consciousness from acute heart failure four months after the end of second course of multipattern botulinum toxin therapy. Found that improvements of the brain functional state against the backdrop of reduced spasticity were observed regardless of primary brain damage origin, level of consciousness and of multipattern botulinum toxin therapy course repeatability. The observed dynamics of neurophysiological indicators had a normalizing direction, some differences associated with the initial level of consciousness. Electrophysiological changes during the improvement of consciousness against the background of multipattern botulinum toxin therapy were not specific. Features of improving energy metabolism in the certain areas of the brain could be caused by just such treatment, and reflected the contribution of pathological sensorimotor integration in maintaining impaired consciousness. Postmortem neuromorphological study of the patient brain identified progenitor stem and proliferating cells and newly formed neurons in brain areas whose in-life functional state was continuously improving, newly formed neurons migrating flow through the corpus callosum and diffuse activation of axonogenesis. We assume that the central effect of multipattern botulinum toxin therapy associated with improvement of consciousness, may be a double. The first is immediate, due to a decrease in pathological afferentation from the muscles, the second - apparently deferred and prolonged, manifested in the activation of functional neurogenesis and axonogenesis in the brain. The continuation of complex multimodal research on the study of post-comatose long-term consciousness disorders seems promising.

Fattening of Young Beef Cattle on Hay Diets

The article presents the results of studies on the use of hayfood rations from perennial legumes prepared in packaging film for feeding young cattle. The diets of feeding young cattle are balanced according to the main elements of nutrition, which made it possible to obtain average daily gains at the level of 10220–1244 grams. The nutritional value of the diets was almost the same in the groups and amounted to 9.33–9.39 energetic feed unit. It was found that animals treated with alfalfa and goat senator digested dry matter better by 7.83 and 3.4 %, crude protein by 5.41 and 1.87 %; crude fat by 19.89 and 4.67 %, crude fiber by 16.46 and 14.10 % compared with calves receiving clover hay, respectively. Using silage diets from these crops improves energy metabolism. The coefficient of productive use of metabolic energy by animals of the 3rd experimental group was 43.91 %, which is 5.15 % more than in the 1st experimental group, by 8.60 % from the 2nd experimental group. Animals of the 3 experimental groups were characterized by a higher slaughter yield, in comparison with other groups. The cost of feed per unit of increase in live weight of animals in group 2 was 9.19 energetic feed unit, which is 0.9 energetic feed unit and 1.73 energetic feed unit less than in 1 and 3 groups.

Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UHPLC-Q-TOF/MS Combined with Multivariate Statistical Analysis.

Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography–tandem quadrupole/time-of-flight mass spectrometry (UHPLC–Q–TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2–ketobutyric acid, 3–hexenedioic acid, but–2–enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2–ketobutyric acid, 3–hexenedioic acid, but–2–enoic acid, argininic acid, galactonic acid, lactic acid, equol 4′–O–glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1–phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3–dehydrocarnitine, m–methylhippuric acid, 3–hydroxyoctanoic acid, p–cresol sulfate, estriol 3–sulfate 16–glucuronide, 10–hydroxy–9–(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.

Effect of a single bout of resistance exercise on zinc-α2-glycoprotein

Context Resistance exercise training has recently been considered as an effective type of training to increase energy metabolism and insulin sensitivity. However, mechanisms of the resistance training-induced improvements in energy metabolism and insulin sensitivity have not been fully understood. Zinc-α2-glycoprotein (ZAG), which is a novel adipokine, has beneficial effects on energy metabolism and insulin sensitivity. Objective We investigated the effect of a single bout of resistance exercise on the ZAG concentration. Methods Nine healthy men were enrolled. They performed a single bout of resistance exercise (bench press and leg press) consisting of 10 repetitions of five sets at 70% of maximum strength with 90-s rests in between sets. Blood samples were obtained before and after acute resistance exercise to measure the ZAG concentration. Results The serum ZAG concentration significantly increased following acute resistance exercise. Conclusion This result suggests that a single bout of resistance exercise may enhance the ZAG concentration.

Pre-hypoxia exposure inhibited copper toxicity by improving energy metabolism, antioxidant defence and mitophagy in the liver of the large yellow croaker Larimichthys crocea

This study investigated the effects of moderate hypoxia pre-exposure on energy metabolism, antioxidant defence and mitophagy in the liver of the large yellow croaker Larimichthys crocea exposed to Cu. Fish were pre-exposed to either normoxia or hypoxia (~3.0 mg L−1, 42% O2 saturation) for 48 h, and subsequently were subjected to either control (without Cu addition) or Cu (168 μg L−1) under normoxic conditions for another 48 h. Copper exposure under normoxia induced Cu toxicity that increased mortality, the production of reactive oxygen species (ROS) and malondialdehyde, and aberrant hepatic mitochondrial ultrastructure. Interestingly, hypoxia pre-exposure improved energy metabolism, antioxidant ability and mitophagy response, and reduced the Cu content to inhibit Cu toxicity, reflecting the enhanced survival rate and reduced oxidative damage. In these processes, hypoxia-inducible factor-1α (HIF-1α), transcription factors NFE2-related nuclear factor 2 (Nrf2), and forkhead box O-3 (FoxO3) mRNA levels were correlated with expression of genes related to energy metabolism, antioxidant defence and mitophagy, respectively, indicating HIF-1α, Nrf2, and FoxO3 are required for the induction of their respective target genes. Overall, moderate hypoxia pre-exposure was able to generate adaptive responses to mitigate Cu-induced toxicological effects, underlining a central role of hormesis.

Ginkgolide B for Myocardial Ischemia/Reperfusion Injury: A Preclinical Systematic Review and Meta-Analysis

Ginkgolide B (GB) is an extract of dried Ginkgo biloba leaves and possesses various pharmacological activities in the cardiovascular system. Herein, we aim to assess the available preclinical evidence and possible mechanisms of GB for myocardial ischemia/reperfusion injury. The study quality score was assessed using the CAMARADES 10-item checklist. Rev-Man 5.3 software was used for data analyses. Nineteen studies with total 437 animals were included for analysis. Meta-analyses indicated that GB interventions significantly reduce myocardial infarct size and cardiac markers when compared with control (P < 0.05). The possible mechanisms via which GB exerts cardioprotective effects are mainly associated with anti-oxidation, anti-inflammation, anti-apoptosis, and improvement of energy metabolism. Our study indicates that GB might be a promising cardioprotective agent for myocardial ischemia/reperfusion injury and may contribute to future clinical trial design.

Astragaloside IV alleviates myocardial damage induced by type 2 diabetes via improving energy metabolism.

The aim of the present study was to evaluate the protective effect and mechanism of Astragaloside IV (ASIV) on myocardial injury induced by type 2 diabetes, with a focus on energy metabolism. Blood glucose, the hemodynamic index, left ventricular weight/heart weight (LVW/HW), the left ventricular systolic pressure (LVSP), the left ventricular end diastolic pressure (LVEDP) and cell survival rate were measured in streptozotocin-induced diabetes model rats. Western blot analysis, PCR, hematoxylin-eosin and TUNEL staining, flow cytometry and ELISA were used to detect: i) Cardiomyocyte damage indicators such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cytochrome c (Cyt C), caspase-3, cleaved caspase-3 and the apoptotic rate; ii) energy metabolism indicators such as ATP/AMP and ADP/AMP; and iii) energy metabolism associated pathway proteins such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and nuclear respiratory factor 1 (NRF1). The present demonstrated increased blood glucose, LVW/HW, LVSP, LVEDP and the cardiomyocyte damage indicators (ANP, BNP, Cyt C and caspase-3), in the diabetic and high glucose-treated groups, which were decreased by ASIV. The expression of NRF-1 and PGC-1α significantly changed in the model group and was markedly improved following ASIV treatment. Furthermore, the abnormal energy metabolism in the model group was reversed by ASIV. According to the results, ASIV can regulate energy metabolism by regulating the release of PGC-1α and NRF1 to rescue the abnormal energy metabolism caused by diabetes mellitus, thus decreasing the myocardial damage caused by diabetic cardiomyopathy.

Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice With Mild Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA), an autosomal recessive neurodegenerative disease characterized by the loss of spinal-cord motor-neurons, is caused by mutations on Survival-of-Motor Neuron (SMN)-1 gene. The expression of SMN2, a SMN1 gene copy, partially compensates for SMN1 disruption due to exon-7 excision in 90% of transcripts subsequently explaining the strong clinical heterogeneity. Several alterations in energy metabolism, like glucose intolerance and hyperlipidemia, have been reported in SMA at both systemic and cellular level, prompting questions about the potential role of energy homeostasis and/or production involvement in disease progression. In this context, we have recently reported the tolerance of mild SMA-like mice (SmnΔ7/Δ7; huSMN2+/+) to 10 months of low-intensity running or high-intensity swimming exercise programs, respectively involving aerobic and a mix aerobic/anaerobic muscular metabolic pathways. Here, we investigated whether those exercise-induced benefits were associated with an improvement in metabolic status in mild SMA-like mice. We showed that untrained SMA-like mice exhibited a dysregulation of lipid metabolism with an enhancement of lipogenesis and adipocyte deposits when compared to control mice. Moreover, they displayed a high oxygen consumption and energy expenditure through β-oxidation increase yet for the same levels of spontaneous activity. Interestingly, both exercises significantly improved lipid metabolism and glucose homeostasis in SMA-like mice, and enhanced oxygen consumption efficiency with the maintenance of a high oxygen consumption for higher levels of spontaneous activity. Surprisingly, more significant effects were obtained with the high-intensity swimming protocol with the maintenance of high lipid oxidation. Finally, when combining electron microscopy, respiratory chain complexes expression and enzymatic activity measurements in muscle mitochondria, we found that (1) a muscle-specific decreased in enzymatic activity of respiratory chain I, II, and IV complexes for equal amount of mitochondria and complexes expression and (2) a significant decline in mitochondrial maximal oxygen consumption, were reduced by both exercise programs. Most of the beneficial effects were obtained with the high-intensity swimming protocol. Taking together, our data support the hypothesis that active physical exercise, including high-intensity protocols, induces metabolic adaptations at both systemic and cellular levels, providing further evidence for its use in association with SMN-overexpressing therapies, in the long-term care of SMA patients.

A network pharmacology approach to discover action mechanisms of Yangxinshi Tablet for improving energy metabolism in chronic ischemic heart failure.

Most cardiovascular diseases ultimately result in heart failure, an intractable problem in modern medicine. Yangxinshi tablet (YXS) is a Chinese medicine formula that is used clinically to treat coronary heart disease. However, the active compounds, potential targets, and pharmacological and molecular mechanism of its anti-heart failure activity remain unclear. Therefore, further investigation is required. Active ingredients and potential targets of YXS for treating heart failure have been reported previously. However, the molecular functions or biological processes of YXS in energy metabolism have not been discovered. To date, no experimental study to validate the potential anti-heart failure mechanism of YXS. The aim of this study was to study the therapeutic effect of YXS on rats with chronic ischemic heart failure by evaluating rat cardiac function and exercise tolerance, and to explore its potential mechanism by network pharmacology, western blotting, quantitative RT-PCR and histological analysis. In this investigation, chronic ischemic heart failure rats were randomly assigned to five groups: control group (sham operation), model group (0.5% CMC-Na), trimetazidine group (positive control) and two YXS groups (low- and high-dose groups). Experimental rats were treated by gavage with 10 mg/kg/d (clinical equivalent dose) trimetazidine (TMZ), 500 mg/kg/d (clinical equivalent dose) YXS and 1000 mg/kg/d YXS, respectively, for 5 weeks. The cardiac functions of rats were detected by High-Resolution In Vivo Imaging System. We elucidated novel understanding of the active compounds of YXS in rat plasma and predicted the energy metabolism related targets and processes for heart failure. Then, we validated experimentally the targets and mechanism of YXS on these pathological processes in vivo. It was found that YXS was able to effectively improve cardiac LVIDs, LVEDV, LVESV and EF, decrease myocardial oxygen consumption and reduce myocardial infarct size in rats with chronic ischemic heart failure was similar to that of TMZ. We identified 63 major candidate targets for YXS that are closely to heart failure progression. Enrichment analysis revealed key targets for YXS associated to oxygen delivery, glucose utilization, and mitochondrial biogenesis. Meanwhile, we validated that YXS could promote the expression of downstream HIF-1α, PGC1α and GLUT4 by increasing phosphorylation of PI3K, Akt, mTOR, rpS6 and AMPK. The results show that YXS could activate related PI3K/Akt/mTOR/rpS6/HIF-1α and AMPK/PGC1α/GLUT4 signaling pathways in chronic ischemic heart failure rats. Further experiments demonstrated that YXS increased mitochondrial biogenesis in chronic ischemic heart failure rats and improved exercise tolerance CONCLUSION: YXS treated chronic ischemic heart failure through activating its targets which play pivotal roles in oxygen delivery, glucose utilization and mitochondrial biogenesis to improve energy metabolism through a multi-component, multi-level, multi-target, multi-pathway and multi-mechanism approaches.

NanoFe3O4 accelerates methanogenic straw degradation by improving energy metabolism

The impacts of nanoFe3O4 on the composition of degradation products, microbial community, and microbial metabolic functions during rice straw anaerobic degradation were investigated. Under nanoFe3O4 addition, CH4 production and straw degradation increased by 81% and 10.4%, respectively, in paddy soil enrichment. Coupling product chemistry and microbial community during straw degradation found that nanoFe3O4 effectively promoted the hydrolysis-acidification-methanogenesis of straw, which made lignin-, lipid-, protein-, tannin-like and VFAs products rapidly increase and then quickly decrease. Moreover, the relative abundance of Clostridiaceae and Methanosarcina corresponded with increased hydrolysis and acetoclastic methanogenesis with nanoFe3O4 addition. Cellular processes, environmental information processing and metabolism, especially energy metabolism, were enhanced functions of the microbial community during straw degradation with nanoFe3O4. The nanoFe3O4 addition may improve the electron transfer efficiency, stimulate energy release, reduce Gibbs free energy of the half reaction of organic carbon oxidation (ΔGcox0) and promote energy metabolism to accelerate straw degradation and CH4 generation.

Suppression of Brown Adipocyte Autophagy Improves Energy Metabolism by Regulating Mitochondrial Turnover.

The high abundance of mitochondria and the expression of mitochondrial uncoupling protein 1 (UCP1) confer upon brown adipose tissue (BAT) the unique capacity to convert chemical energy into heat at the expense of ATP synthesis. It was long believed that BAT is present only in infants, and so, it was not considered as a potential therapeutic target for metabolic syndrome; however, the discovery of metabolically active BAT in adult humans has re-stimulated interest in the contributions of BAT metabolic regulation and dysfunction to health and disease. Here we demonstrate that brown adipocyte autophagy plays a critical role in the regulation BAT activity and systemic energy metabolism. Mice deficient in brown adipocyte autophagy due to BAT-specific deletion of Atg7—a gene essential for autophagosome generation—maintained higher mitochondrial content due to suppression of mitochondrial clearance and exhibited improved insulin sensitivity and energy metabolism. Autophagy was upregulated in BAT of older mice compared to younger mice, suggesting its involvement in the age-dependent decline of BAT activity and metabolic rate. These findings suggest that brown adipocyte autophagy plays a crucial role in metabolism and that targeting this pathway may be a potential therapeutic strategy for metabolic syndrome.

Effect of Cocoa Products and Its Polyphenolic Constituents on Exercise Performance and Exercise-Induced Muscle Damage and Inflammation: A Review of Clinical Trials.

In recent years, the consumption of chocolate and, in particular, dark chocolate has been “rehabilitated” due to its high content of cocoa antioxidant polyphenols. Although it is recognized that regular exercise improves energy metabolism and muscle performance, excessive or unaccustomed exercise may induce cell damage and impair muscle function by triggering oxidative stress and tissue inflammation. The aim of this review was to revise the available data from literature on the effects of cocoa polyphenols on exercise-associated tissue damage and impairment of exercise performance. To this aim, PubMed and Web of Science databases were searched with the following keywords: “intervention studies”, “cocoa polyphenols”, “exercise training”, “inflammation”, “oxidative stress”, and “exercise performance”. We selected thirteen randomized clinical trials on cocoa ingestion that involved a total of 200 well-trained athletes. The retrieved data indicate that acute, sub-chronic, and chronic cocoa polyphenol intake may reduce exercise-induced oxidative stress but not inflammation, while mixed results are observed in terms of exercise performance and recovery. The interpretation of available results on the anti-oxidative and anti-inflammatory activities of cocoa polyphenols remains questionable, likely due to the variety of physiological networks involved. Further experimental studies are mandatory to clarify the role of cocoa polyphenol supplementation in exercise-mediated inflammation.

Benefits of dietary supplements on the physical fitness of German Shepherd dogs during a drug detection training course.

A high standard of physical fitness is an essential characteristic of drug detection dogs because it affects not only their ability to sustain high activity levels but also their attention and olfaction efficiency. Nutritional supplements could improve physical fitness by modulating energy metabolism, oxidative processes, and perceived fatigue. The aim of this study was to investigate the physiological and biochemical changes induced by submaximal exercise on drug detection dogs (German Shepherd breed) and to assess whether a dietary supplement improves their physical fitness. During a drug detection dog training course, seven dogs were fed with a basal diet (Control Group) for three-month period, while a further seven dogs were fed with a basal diet as well as a daily nutritional supplement containing branched-chain and limiting amino acids, carnitine, vitamins, and octacosanol (Treatment Group). At the end of this period, individual physical fitness was assessed by making each subject take a graded treadmill exercise test. A human heart rate monitor system was used to record the dog’s heart rate (HR) during the treadmill exercise and the subsequent recovery period. The parameters related to HR were analysed using nonparametric statistics. Blood samples were collected before starting the nutritional supplement treatment, before and after the treadmill exercise and following recovery. Linear mixed models were used. The dietary supplements accelerated HR recovery, as demonstrated by the lower HR after recovery (P<0.05) and Time constants of HR decay (P<0.05), and by the higher Absolute HR Recovered (P<0.05) recorded in the Treatment group compared with the Control dogs. The supplemented dogs showed the lowest concentrations of creatine kinase (CK; P<0.001), aspartate aminotransferase (AST, P<0.05) and non-esterified fatty acids (NEFA; P<0.01) suggesting a reduction in muscle damage and improvement of energy metabolism. These data suggest that this combined supplement can significantly enhance the physical fitness of drug detection dogs.