scholarly journals Cardioprotective responses to aerobic exercise-induced physiological hypertrophy in zebrafish heart

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Zhanglin Chen ◽  
Zuoqiong Zhou ◽  
Xiyang Peng ◽  
Chenchen Sun ◽  
Dong Yang ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Myocardial Hypertrophy ◽  
Acid Oxidation ◽  
Mtor Signaling Pathway ◽  
Fission Event ◽  
Mitochondrial Homeostasis ◽  
Expression Of Genes ◽  
Exercise Induced ◽  
Physiological Hypertrophy ◽  
Zebrafish Heart

AbstractHerein, we aimed to establish an aerobic exercise-induced physiological myocardial hypertrophy zebrafish (Danio rerio) model and to explore the underlying molecular mechanism. After 4 weeks of aerobic exercise, the AMR and Ucrit of the zebrafish increased and the hearts were enlarged, with thickened myocardium, an increased number of myofilament attachment points in the Z-line, and increased compaction of mitochondrial cristae. We also found that the mTOR signaling pathway, angiogenesis, mitochondrial fusion, and fission event, and mitochondrial autophagy were associated with the adaptive changes in the heart during training. In addition, the increased mRNA expression of genes related to fatty acid oxidation and antioxidation suggested that the switch of energy metabolism and the maintenance of mitochondrial homeostasis induced cardiac physiological changes. Therefore, the zebrafish heart physiological hypertrophy model constructed in this study can be helpful in investigating the cardioprotective mechanisms in response to aerobic exercise.

scholarly journals Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 198
Author(s):  
Bailey A. Loving ◽  
Maoping Tang ◽  
Mikaela C. Neal ◽  
Sachi Gorkhali ◽  
Robert Murphy ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Cholesterol Efflux ◽  
Acid Oxidation ◽  
Lipid Uptake ◽  
Expression Of Genes ◽  
Ppar Signaling ◽  
Ppar Agonists ◽  
Inflammatory State ◽  
Excessive Secretion ◽  
Efflux Pathway

Microglia become increasingly dysfunctional with aging and contribute to the onset of neurodegenerative disease (NDs) through defective phagocytosis, attenuated cholesterol efflux, and excessive secretion of pro-inflammatory cytokines. Dysfunctional microglia also accumulate lipid droplets (LDs); however, the mechanism underlying increased LD load is unknown. We have previously shown that microglia lacking lipoprotein lipase (LPL KD) are polarized to a pro-inflammatory state and have impaired lipid uptake and reduced fatty acid oxidation (FAO). Here, we also show that LPL KD microglia show excessive accumulation of LD-like structures. Moreover, LPL KD microglia display a pro-inflammatory lipidomic profile, increased cholesterol ester (CE) content, and reduced cholesterol efflux at baseline. We also show reduced expression of genes within the canonical cholesterol efflux pathway. Importantly, PPAR agonists (rosiglitazone and bezafibrate) rescued the LD-associated phenotype in LPL KD microglia. These data suggest that microglial-LPL is associated with lipid uptake, which may drive PPAR signaling and cholesterol efflux to prevent inflammatory lipid distribution and LD accumulation. Moreover, PPAR agonists can reverse LD accumulation, and therefore may be beneficial in aging and in the treatment of NDs.

scholarly journals Bioenergetic defects in muscle fibers of RYR1 mutant knock-in mice associated with malignant hyperthermia

2020 ◽  
Vol 295 (45) ◽  
pp. 15226-15235 ◽  
Author(s):  
Leon Chang ◽  
Xiaochen Liu ◽  
Christine P. Diggle ◽  
John P. Boyle ◽  
Philip M. Hopkins ◽  
...  
Keyword(s):  
Mouse Model ◽  
Oxidative Phosphorylation ◽  
Malignant Hyperthermia ◽  
Receptor Gene ◽  
Muscle Fibers ◽  
Acid Oxidation ◽  
Mouse Muscle ◽  
Metabolic Defects ◽  
Expression Of Genes ◽  
Consumption Rates

Mutations in the skeletal muscle ryanodine receptor gene (RYR1) can cause susceptibility to malignant hyperthermia (MH), a potentially lethal genetic condition triggered by volatile anesthetics. MH is associated with hypermetabolism, which has directed research interest into oxidative phosphorylation and muscle bioenergetics. The most common cause of MH in the United Kingdom is the c.7300G>A RYR1 variant, which is present in ∼16% of MH families. Our study focuses on the MH susceptible G2435R-RYR1 knock-in mouse model, which is the murine equivalent of the human c.7300G>A genotype. Using a combination of transcriptomics, protein expression, and functional analysis, we investigated adult muscle fiber bioenergetics in this mouse model. RNA-Seq data showed reduced expression of genes associated with mitochondria and fatty acid oxidation in RYR1 mutants when compared with WT controls. Mitochondrial function was assessed by measuring oxygen consumption rates in permeabilized muscle fibers. Comparisons between WT and homozygous G2435R-RYR1 mitochondria showed a significant increase in complex I–facilitated oxidative phosphorylation in mutant muscle. Furthermore, we observed a gene-dose-specific increase in reactive oxygen species production in G2435R-RYR1 muscle fibers. Collectively, these findings provide evidence of metabolic defects in G2435R-RYR1 knock-in mouse muscle under basal conditions. Differences in metabolic profile could be the result of differential gene expression in metabolic pathways, in conjunction with mitochondrial damage accumulated from chronic exposure to increased oxidative stress.

Swim-exercised mice show a decreased level of protein O-GlcNAcylation and expression of O-GlcNAc transferase in heart

2011 ◽  
Vol 111 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Darrell D. Belke
Keyword(s):  
Protein Interactions ◽  
Contractile Function ◽  
Cell Physiology ◽  
Protein Protein Interactions ◽  
Training Exercise ◽  
General Protein ◽  
Exercise Induced ◽  
Glcnac Transferase ◽  
The Impact ◽  
Physiological Hypertrophy

Swim-training exercise in mice leads to cardiac remodeling associated with an improvement in contractile function. Protein O-linked N-acetylglucosamine ( O-GlcNAcylation) is a posttranslational modification of serine and threonine residues capable of altering protein-protein interactions affecting gene transcription, cell signaling pathways, and general cell physiology. Increased levels of protein O-GlcNAcylation in the heart have been associated with pathological conditions such as diabetes, ischemia, and hypertrophic heart failure. In contrast, the impact of physiological exercise on protein O-GlcNAcylation in the heart is currently unknown. Swim-training exercise in mice was associated with the development of a physiological hypertrophy characterized by an improvement in contractile function relative to sedentary mice. General protein O-GlcNAcylation was significantly decreased in swim-exercised mice. This effect was mirrored in the level of O-GlcNAcylation of individual proteins such as SP1. The decrease in protein O-GlcNAcylation was associated with a decrease in the expression of O-GlcNAc transferase (OGT) and glutamine-fructose amidotransferase (GFAT) 2 mRNA. O-GlcNAcase (OGA) activity was actually lower in swim-trained than sedentary hearts, suggesting that it did not contribute to the decreased protein O-GlcNAcylation. Thus it appears that exercise-induced physiological hypertrophy is associated with a decrease in protein O-GlcNAcylation, which could potentially contribute to changes in gene expression and other physiological changes associated with exercise.

The influence of vigorous aerobic exercise on serum brain-derived neurotrophic factor and estradiol in young, healthy women as a function of the menstrual cycle

2021 ◽  
Author(s):  
Sarah Ahmad ◽  
Rodney Hansen ◽  
Matthew Schmolesky
Keyword(s):  
Menstrual Cycle ◽  
Aerobic Exercise ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Cycle Exercise ◽  
Acute Bout ◽  
Healthy Women ◽  
Exercise Induced ◽  
Induced Changes ◽  
Serum Bdnf

AbstractResearch suggests strong inter-relationships between physical exercise, levels of brain-derived neurotrophic factor (BDNF), levels of estrogen, and the menstrual cycle, and yet no single study has examined these factors collectively in humans. The current study assessed the effect of an acute bout of vigorous aerobic exercise (20 minutes of stationary cycling at 80% of heart rate reserve) on serum BDNF and estradiol in healthy, eumenorrheic women, ages 18-28. In addition, this study determined whether basal BDNF or the exercise-induced increase in BDNF varies throughout the menstrual cycle. Thirty-four subjects were assigned to an experimental (n = 27) or control condition (n = 7). Exercise transiently increased both estradiol (51.2%) and BDNF (23.6%), and basal levels of BDNF and estradiol predicted the magnitude of the exercise-induced increases. Basal BDNF did not vary significantly throughout the menstrual cycle. Exercise-induced changes in BDNF did not correlate with menstrual cycle day or basal estradiol. Basal estradiol and basal BDNF showed a marginally significant positive correlation. Taken together, these results indicate that brief, vigorous aerobic exercise is sufficient to elevate both BDNF and estradiol in healthy women and that the menstrual cycle dramatically influences the magnitude of exercise-induced changes in estradiol, but not BDNF

Effects of the oral hypoglycemic agent methyl palmoxirate on exercise capacity of rats

1984 ◽  
Vol 62 (7) ◽  
pp. 815-818 ◽  
Author(s):  
J. C. Young ◽  
J. E. Bryan ◽  
S. H. Constable ◽  
G. F. Tutwiler ◽  
J. O. Holloszy
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Exercise Capacity ◽  
Liver Glycogen ◽  
Oral Hypoglycemic Agent ◽  
Strenuous Exercise ◽  
Acid Oxidation ◽  
Hypoglycemic Agent ◽  
Minimal Treatment ◽  
Exercise Induced

The effect of the oral hypoglycemic agent methyl palmoxirate (methyl 2-tetradecylglycidate, McN-3716), a selective inhibitor of long chain fatty acid oxidation, on the exercise capacity of normal rats was evaluated. Daily administration of 2.5 mg/kg for 7 days, or of a single dose of 10 mg/kg, of methyl palmoxirate did not affect the ability of rats to perform strenuous exercise of an intensity that caused exhaustion in less than 30 min. The ability to perform prolonged, moderately strenuous exercise of an intensity that could be maintained for more than 60 min was decreased slightly (17%) in the methyl palmoxirate treated rats. This effect appeared to be mediated by a significant reduction in initial liver glycogen content in the methyl palmoxirate treated rats. As a consequence, the methyl palmoxirate treated rats became hypoglycemic during prolonged exercise. Inhibition of fatty acid oxidation in skeletal muscle was minimal. Treatment with methyl palmoxirate protected against the development of exercise-induced ketosis. It appears that the liver is the major site of action of methyl palmoxirate when given in low dosage.

Abstract P095: Aerobic Exercise Training Reduces Endothelin-1-mediated Vasoconstriction In Postmenopausal Women

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Megan M Wenner ◽  
Caitlin Dow ◽  
Jared Greiner ◽  
Brian Stauffer ◽  
Christopher Desouza
Keyword(s):  
Exercise Training ◽  
Aerobic Exercise ◽  
Postmenopausal Women ◽  
Exercise Intervention ◽  
Aerobic Exercise Training ◽  
Receptor Blockade ◽  
Maximal Heart Rate ◽  
Endothelin 1 ◽  
Vasodilator Response ◽  
Exercise Induced

Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in postmenopausal women (PMW), contributing to their increased cardiovascular risk. Although aerobic exercise is beneficial in reducing ET-1 system activity in men, it is unknown whether this favorable vascular effect is conferred in women. In fact, contrary to men, it is uncertain whether aerobic exercise training improves endothelial dysfunction in PMW. We tested the hypothesis that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. We further hypothesized reductions in ET-1 vasoconstrictor tone underly exercise-induced improvements in endothelium-dependent vasodilatation in PMW. Methods: Forearm blood flow (FBF) responses to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol/min for 60 min), acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) in the absence and presence of ET A receptor blockade and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) were determined before and after a 12-week aerobic exercise training intervention in 20 healthy, sedentary PMW (56 + 1 yr). Results: All 20 PMW completed the exercise intervention, walking an average of 4.9 + 0.1 d/wk for 50 + 2 min/d at 71 + 1% of maximal heart rate. After the exercise intervention, BQ-123 elicited no significant change in resting FBF in the previously sedentary PMW compared with significant vasodilation (~25%) before exercise. FBF responses to acetylcholine were markedly higher (~25%; P<0.05) after (from 4.3 + 0.3 to 13.8 + 0.8 mL/100 ml tissue/min) vs before (from 4.1 + 0.2 to 11.3 + 0.8 mL/100 ml tissue/min) exercise training. Moreover, before exercise training the co-infusion of BQ-123 with acetylcholine enhanced (~25%; P<0.05) the vasodilator response (from 4.3 + 0.3 to 13.7 + 0.7 mL/100 mL tissue/min) compared with acetylcholine alone; after exercise training, the presence of BQ-123 did not significantly affect the vasodilator response to acetylcholine. Conclusions: These data demonstrate that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. Furthermore, decreased ET-1-mediated vasoconstriction is an important mechanism underlying aerobic exercise-induced improvement in endothelium-dependent vasodilation in PMW.

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