scholarly journals Exercise training increases mitochondrial biogenesis in the brain

2011 ◽  
Vol 111 (4) ◽  
pp. 1066-1071 ◽  
Author(s):  
Jennifer L. Steiner ◽  
E. Angela Murphy ◽  
Jamie L. McClellan ◽  
Martin D. Carmichael ◽  
J. Mark Davis
Keyword(s):  
Exercise Training ◽  
Mitochondrial Biogenesis ◽  
Citrate Synthase ◽  
Brain Mitochondria ◽  
Brain Regions ◽  
Treadmill Running ◽  
Endurance Capacity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Age Related

Increased muscle mitochondria are largely responsible for the increased resistance to fatigue and health benefits ascribed to exercise training. However, very little attention has been given to the likely benefits of increased brain mitochondria in this regard. We examined the effects of exercise training on markers of both brain and muscle mitochondrial biogenesis in relation to endurance capacity assessed by a treadmill run to fatigue (RTF) in mice. Male ICR mice were assigned to exercise (EX) or sedentary (SED) conditions ( n = 16–19/group). EX mice performed 8 wk of treadmill running for 1 h/day, 6 days/wk at 25 m/min and a 5% incline. Twenty-four hours after the last training bout a subgroup of mice ( n = 9–11/group) were euthanized, and brain (brain stem, cerebellum, cortex, frontal lobe, hippocampus, hypothalamus, and midbrain) and muscle (soleus) tissues were isolated for analysis of mRNA expression of peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1α), Silent Information Regulator T1 (SIRT1), citrate synthase (CS), and mitochondrial DNA (mtDNA) using RT-PCR. A different subgroup of EX and SED mice ( n = 7–8/group) performed a treadmill RTF test. Exercise training increased PGC-1α, SIRT1, and CS mRNA and mtDNA in most brain regions in addition to the soleus ( P < 0.05). Mean treadmill RTF increased from 74.0 ± 9.6 min to 126.5 ± 16.1 min following training ( P < 0.05). These findings suggest that exercise training increases brain mitochondrial biogenesis, which may have important implications, not only with regard to fatigue, but also with respect to various central nervous system diseases and age-related dementia that are often characterized by mitochondrial dysfunction.

The Effect of Aerobic Exercise on Deteriorating VO2max and Diminished Mitochondrial Biogenesis During Aging

2021 ◽  
Vol 15 (12) ◽  
pp. 3462-3466
Author(s):  
Eda Akkiz Ağaşcioğlu ◽  
Ofcan Oflaz
Keyword(s):  
Aerobic Exercise ◽  
Mitochondrial Biogenesis ◽  
Vital Capacity ◽  
Antioxidant Activities ◽  
Reduction Rate ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Physiological Level ◽  
Cellular Environment ◽  
Age Related

Aging seems to be inevitable and gradual loss of physical activity is associated with frailty and many age-related disorders. Exercise is the way of keeping a healthy life and delaying aging process. Deterioration in pulmonary vital capacity is inevitable, and mitochondrial biogenesis also diminishes with aging. Regular aerobic exercise alleviates the diminishing vital capacity while increasing mitochondrial biogenesis in aging. Peroxisome proliferator-activated receptor c coactivator 1 alpha (PGC-1a), which is the master regulator of mitochondrial biogenesis, is activated by reactive oxygen species (ROS). Exercise-induced lactate leads to formation of ROS and synthesis of nitric oxide (NO) at physiological level. PGC1a regulation by NO seems to be controversial. Over the physiological limit of ROS and NO has toxic effects in cellular environment with reduced antioxidant activities in aging. Overall, exercise seems to be beneficial option to alleviate reduction rate of vital capacity and to enhance mitochondrial biogenesis via lactate-induced ROS formation. Keywords: Aging, Exercise, Maximum oxygen consumption rate, Lungs vital capacity, Mitochondria Biogenesis.

scholarly journals Exercise Training-Induced PPARβ Increases PGC-1α Protein Stability and Improves Insulin-Induced Glucose Uptake in Rodent Muscles

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 652 ◽  
Author(s):  
Ju-Sik Park ◽  
John O. Holloszy ◽  
Kijin Kim ◽  
Jin-Ho Koh
Keyword(s):  
Cytochrome C ◽  
Exercise Training ◽  
Protein Stability ◽  
Glucose Uptake ◽  
Citrate Synthase ◽  
Peroxisome Proliferator ◽  
Mitochondrial Enzymes ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor

This study aimed to investigate the long-term effects of training intervention and resting on protein expression and stability of peroxisome proliferator-activated receptor β/δ (PPARβ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α), glucose transporter type 4 (GLUT4), and mitochondrial proteins, and determine whether glucose homeostasis can be regulated through stable expression of these proteins after training. Rats swam daily for 3, 6, 9, 14, or 28 days, and then allowed to rest for 5 days post-training. Protein and mRNA levels were measured in the skeletal muscles of these rats. PPARβ was overexpressed and knocked down in myotubes in the skeletal muscle to investigate the effects of swimming training on various signaling cascades of PGC-1α transcription, insulin signaling, and glucose uptake. Exercise training (Ext) upregulated PPARβ, PGC-1α, GLUT4, and mitochondrial enzymes, including NADH-ubiquinone oxidoreductase (NUO), cytochrome c oxidase subunit I (COX1), citrate synthase (CS), and cytochrome c (Cyto C) in a time-dependent manner and promoted the protein stability of PPARβ, PGC-1α, GLUT4, NUO, CS, and Cyto C, such that they were significantly upregulated 5 days after training cessation. PPARβ overexpression increased the PGC-1α protein levels post-translation and improved insulin-induced signaling responsiveness and glucose uptake. The present results indicate that Ext promotes the protein stability of key mitochondria enzymes GLUT4, PGC-1α, and PPARβ even after Ext cessation.

Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle

2011 ◽  
Vol 301 (1) ◽  
pp. R67-R75 ◽  
Author(s):  
Brendon J. Gurd ◽  
Yuko Yoshida ◽  
Jay T. McFarlan ◽  
Graham P. Holloway ◽  
Chris D. Moyes ◽  
...  
Keyword(s):  
Protein Content ◽  
Mitochondrial Biogenesis ◽  
Acute Exercise ◽  
Citrate Synthase ◽  
Human Muscle ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Of Genes ◽  
Whole Muscle ◽  
Type Information

Silent mating type information regulator 2 homolog 1 (SIRT1)-mediated peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) deacetylation is potentially key for activating mitochondrial biogenesis. Yet, at the whole muscle level, SIRT1 is not associated with mitochondrial biogenesis (Gurd, BJ, Yoshida Y, Lally J, Holloway GP, Bonen A. J Physiol 587: 1817–1828, 2009). Therefore, we examined nuclear SIRT1 protein and activity in muscle with varied mitochondrial content and in response to acute exercise. We also measured these parameters after stimulating mitochondrial biogenesis with chronic muscle contraction and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration in rodents and exercise training in humans. In skeletal and heart muscles, nuclear SIRT1 protein was negatively correlated with indices of mitochondrial density (citrate synthase activity, CS; cytochrome oxidase IV, COX IV), but SIRT1 activity was positively correlated with these parameters ( r > 0.98). Acute exercise did not alter nuclear SIRT1 protein but did induce a time-dependent increase in nuclear SIRT1 activity. This increase in SIRT1 activity was temporally related to increases in mRNA expression of genes activated by PGC-1α. Both chronic muscle stimulation and AICAR increased mitochondrial biogenesis and muscle PGC-1α, but not nuclear PGC-1α. Concomitantly, muscle and nuclear SIRT1 protein contents were reduced, but nuclear SIRT1 activity was increased. In human muscle, training-induced mitochondrial biogenesis did not alter muscle or nuclear SIRT1 protein content, but it did increase muscle and nuclear PGC-1α and SIRT1 activity. Thus, nuclear SIRT1 activity, but not muscle or nuclear SIRT1 protein content, is associated with contraction-stimulated mitochondrial biogenesis in rat and human muscle, possibly via AMPK activation.

scholarly journals Invalidation of the Transcriptional Modulator of Lipid Metabolism PPARβ/δ in T Cells Prevents Age-Related Alteration of Body Composition and Loss of Endurance Capacity

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne-Sophie Rousseau ◽  
Joseph Murdaca ◽  
Gwenaëlle Le Menn ◽  
Brigitte Sibille ◽  
Walter Wahli ◽  
...  
Keyword(s):  
T Cells ◽  
Body Composition ◽  
Cell Metabolism ◽  
Acid Oxidation ◽  
Endurance Capacity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Age Related ◽  
Effects Of Aging ◽  
Original Potential

Anti-inflammatory regulatory T cells (Tregs) are the most metabolically flexible CD4+ T cells by using both glycolysis and fatty acid oxidation (FAO) which allow them to migrate in tissues. With aging, Tregs accumulate in secondary lymphoid organs and are involved in impairment of skeletal muscle (SKM) regeneration and mass maintenance. In this study, we showed that a deletion of a FAO modulator, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), specifically in T cells (KO-T PPARβ/δ), increased the number of CD4+ T cells at day 2 following a cardiotoxin-induced SKM regeneration. Older KO-T PPARβ/δ mice maintained a Tregs prevalence in lymph nodes similar to young mice. Surprisingly, KO-T PPARβ/δ mice were protected from the effects of age on lean and fat mass and endurance capacity. Our results lead us to propose an original potential role of T cell metabolism in the effects of aging on the maintenance of body composition and endurance capacity.

Myosin heavy chain composition in the rat diaphragm: effect of age and exercise training

1992 ◽  
Vol 73 (4) ◽  
pp. 1282-1286 ◽  
Author(s):  
L. E. Gosselin ◽  
M. Betlach ◽  
A. C. Vailas ◽  
M. L. Greaser ◽  
D. P. Thomas
Keyword(s):  
Exercise Training ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Citrate Synthase ◽  
Relative Proportion ◽  
Maximal Oxygen Consumption ◽  
Age Groups ◽  
Treadmill Running ◽  
Age Related ◽  
Effects Of Aging

Increases in aerobic capacity in both young and senescent rats consequent to endurance exercise training are now known to occur not only in locomotor skeletal muscle but also in diaphragm. In the current study the effects of aging and exercise training on the myosin heavy chain (MHC) composition were determined in both the costal and crural diaphragm regions of female Fischer 344 rats. Exercise training [treadmill running at 75% maximal oxygen consumption (1 h/day, 5 day/wk, x 10 wk)] resulted in similar increases in plantaris muscle citrate synthase activity in both young (5 mo) and old (23 mo) trained animals (P < 0.05). Computerized densitometric image analysis of fast and slow MHC bands revealed the ratio of fast to slow MHC to be significantly higher (P < 0.005) in the crural compared with costal diaphragm region in both age groups. In addition, a significant age-related increase (P < 0.05) in percentage of slow MHC was observed in both diaphragm regions. However, exercise training failed to change the relative proportion of slow MHC in either the costal or crural region.

scholarly journals Effects of Exercise Training on Renal Carnitine Biosynthesis and Uptake in the High-Fat and High-Sugar-Fed Mouse

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2100
Author(s):  
Aman Upadhyay ◽  
Layla Al-Nakkash ◽  
Tom L. Broderick
Keyword(s):  
Exercise Training ◽  
Organic Cation Transporter ◽  
Treadmill Running ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
High Sugar ◽  
Background Diet ◽  
Organic Cation Transporter 2

(1) Background: Diet-induced obesity inhibits hepatic carnitine biosynthesis. Herein, the effects of high-fat (HF) and high-sugar (HFHS) feeding and exercise training (ET) on renal carnitine biosynthesis and uptake were determined. (2) Methods: Male C57BL/6J mice were assigned to the following groups: lean control (standard chow), HFHS diet, and HFHS diet with ET. ET consisted of 150 min of treadmill running per week for 12 weeks. Protein levels of γ-butyrobetaine hydroxylase (γ-BBH) and organic cation transporter-2 (OCTN2) were measured as markers of biosynthesis and uptake, respectively. (3) Results: HFHS feeding induced an obese diabetic state with accompanying hypocarnitinemia, reflected by decreased free carnitine levels in plasma and kidney. This hypocarnitinemia was associated with decreased γ-BBH (~30%) and increased OCTN2 levels (~50%). ET failed to improve the obesity and hyperglycemia, but improved insulin levels and prevented the hypocarnitinemia. ET increased protein levels of γ-BBH, whereas levels of OCTN2 were decreased. Peroxisome proliferator-activated receptor-alpha content was not changed by the HFHS diet or ET. (4) Conclusions: Our results indicate that ET prevents the hypocarnitinemia induced by HFHS feeding by increasing carnitine biosynthesis in kidney. Increased expression of OCTN2 with HFHS feeding suggests that renal uptake was stimulated to prevent carnitine loss.

Central role of nitric oxide synthase in AICAR and caffeine-induced mitochondrial biogenesis in L6 myocytes

2010 ◽  
Vol 108 (3) ◽  
pp. 589-595 ◽  
Author(s):  
G. K. McConell ◽  
G. P. Y. Ng ◽  
M. Phillips ◽  
Z. Ruan ◽  
S. L. Macaulay ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mitochondrial Biogenesis ◽  
Calcium Release ◽  
Citrate Synthase ◽  
Peroxisome Proliferator ◽  
No Donor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Calcium Dependent ◽  
L6 Myotubes ◽  
Cox 1

5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR) and caffeine, which activate AMP-activated protein kinase (AMPK) and cause sarcoplasmic reticulum calcium release, respectively, have been shown to increase mitochondrial biogenesis in L6 myotubes. Nitric oxide (NO) donors also increase mitochondrial biogenesis. Since neuronal and endothelial NO synthase (NOS) are calcium dependent and are also phosphorylated by AMPK, we hypothesized that NOS inhibition would attenuate the activation of mitochondrial biogenesis in response to AICAR and caffeine. L6 myotubes either were not treated (control) or were exposed acutely or for 5 h/day over 5 days to 100 μM of NG-nitro-l-arginine methyl ester (l-NAME, NOS inhibitor), 100 μM S-nitroso- N-acetyl-penicillamine (SNAP) (NO donor) ± 100 μM l-NAME, 2 mM AICAR ± 100 μM l-NAME, or 5 mM caffeine ± 100 μM l-NAME ( n = 12/treatment). Acute AICAR administration increased ( P < 0.05) phospho- (P-)AMPK, but also increased P-CaMK, with resultant chronic increases in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), cytochrome- c oxidase (COX)-1, and COX-4 protein expression compared with control cells. NOS inhibition, which had no effect on AICAR-stimulated P-AMPK, surprisingly increased P-CaMK and attenuated the AICAR-induced increases in COX-1 and COX-4 protein. Caffeine administration, which increased P-CaMK without affecting P-AMPK, increased COX-1, COX-4, PGC-1α, and citrate synthase activity. NOS inhibition, surprisingly, greatly attenuated the effect of caffeine on P-CaMK and attenuated the increases in COX-1 and COX-4 protein. SNAP increased all markers of mitochondrial biogenesis, and it also increased P-AMPK and P-CaMK. In conclusion, AICAR and caffeine increase mitochondrial biogenesis in L6 myotubes, at least in part, via interactions with NOS.

PGC-1α-mediated regulation of mitochondrial function and physiological implications

2020 ◽  
Vol 45 (9) ◽  
pp. 927-936
Author(s):  
Jens Frey Halling ◽  
Henriette Pilegaard
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Control Mechanisms ◽  
Peroxisome Proliferator Activated Receptor ◽  
Age Related ◽  
Mitochondrial Functions

The majority of human energy metabolism occurs in skeletal muscle mitochondria emphasizing the importance of understanding the regulation of myocellular mitochondrial function. The transcriptional co-activator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) has been characterized as a major factor in the transcriptional control of several mitochondrial components. Thus, PGC-1α is often described as a master regulator of mitochondrial biogenesis as well as a central player in regulating the antioxidant defense. However, accumulating evidence suggests that PGC-1α is also involved in the complex regulation of mitochondrial quality beyond biogenesis, which includes mitochondrial network dynamics and autophagic removal of damaged mitochondria. In addition, mitochondrial reactive oxygen species production has been suggested to regulate skeletal muscle insulin sensitivity, which may also be influenced by PGC-1α. This review aims to highlight the current evidence for PGC-1α-mediated regulation of skeletal muscle mitochondrial function beyond the effects on mitochondrial biogenesis as well as the potential PGC-1α-related impact on insulin-stimulated glucose uptake in skeletal muscle. Novelty PGC-1α regulates mitochondrial biogenesis but also has effects on mitochondrial functions beyond biogenesis. Mitochondrial quality control mechanisms, including fission, fusion, and mitophagy, are regulated by PGC-1α. PGC-1α-mediated regulation of mitochondrial quality may affect age-related mitochondrial dysfunction and insulin sensitivity.

Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats

2008 ◽  
Vol 294 (5) ◽  
pp. H2121-H2128 ◽  
Author(s):  
Zoltan Ungvari ◽  
Nazar Labinskyy ◽  
Sachin Gupte ◽  
Praveen N. Chander ◽  
John G. Edwards ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mitochondrial Biogenesis ◽  
Cell Metabolism ◽  
Cellular Aging ◽  
Peroxisome Proliferator ◽  
Ros Production ◽  
Peroxisome Proliferator Activated Receptor ◽  
Altered Expression ◽  
Age Related ◽  
Mitochondrial Ros

Mitochondrial biogenesis is involved in the control of cell metabolism, signal transduction, and regulation of mitochondrial reactive oxygen species (ROS) production. Despite the central role of mitochondria in cellular aging and endothelial physiology, there are no studies extant investigating age-related alterations in mitochondrial biogenesis in blood vessels. Electronmicroscopy and confocal microscopy (en face Mitotracker staining) revealed that in aortas of F344 rats, a decline in mitochondrial biogenesis occurs with aging. In aged vessels, the expression of the mitochondrial biogenesis factors (including mitochondrial transcription factor A and peroxisome proliferator-activated receptor-γ coactivator-1) was decreased. The vascular expression of complex I, III, and IV significantly declined with age, whereas aging did not alter the expression of complex II and V. Cytochrome c oxidase (COX) expression/activity exhibited the greatest age-related decline, which was associated with increased mitochondrial ROS production in the aged vessels. In cultured coronary arterial endothelial cells, a partial knockdown of COX significantly increased mitochondrial ROS production. In conclusion, vascular aging is characterized by a decline in mitochondrial mass in the endothelial cells and an altered expression of components of the mitochondrial electron transport chain likely due to a dysregulation of mitochondrial biogenesis factors. We posit that impaired mitochondrial biogenesis and downregulation of COX may contribute to the increased mitochondrial oxidative stress in aged endothelial cells.

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