scholarly journals PGC-1α is Dispensable for Exercise-Induced Mitochondrial Biogenesis in Skeletal Muscle

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41817 ◽  
Author(s):  
Glenn C. Rowe ◽  
Riyad El-Khoury ◽  
Ian S. Patten ◽  
Pierre Rustin ◽  
Zolt Arany
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Exercise Induced

Exercise-Induced Mitochondrial Biogenesis in Skeletal Muscle

2007 ◽  
pp. 37-60 ◽  
Author(s):  
David A. Hood ◽  
Beatrice Chabi ◽  
Keir Menzies ◽  
Michael O’Leary ◽  
Donald Walkinshaw
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Exercise Induced

Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle

2007 ◽  
Vol 102 (1) ◽  
pp. 314-320 ◽  
Author(s):  
G. D. Wadley ◽  
G. K. McConell
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Acute Exercise ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced ◽  
Edl Muscle ◽  
Oxide Synthase

The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no l-NAME ingestion and acute exercise, rest plus l-NAME, and rest without l-NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly ( P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) mRNA levels and tended ( P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or β-hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL.

scholarly journals Forty high-intensity interval training sessions blunt exercise-induced changes in the nuclear protein content of PGC-1α and p53 in human skeletal muscle

2019 ◽  
Author(s):  
Cesare Granata ◽  
Rodrigo S.F. Oliveira ◽  
Jonathan P. Little ◽  
David J. Bishop
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Mitochondrial Biogenesis ◽  
Exercise Intensity ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Interval Training ◽  
High Intensity Interval Training ◽  
High Intensity Interval ◽  
Exercise Induced

ABSTRACTExercise-induced increases in peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and p53 protein content in the nucleus mediate the initial phase of exercise-induced mitochondrial biogenesis. Here we investigated if exercise-induced increases in these and other markers of mitochondrial biogenesis were altered after 40 sessions of twice-daily high-volume high-intensity interval training (HVT) in human skeletal muscle. Vastus lateralis muscle biopsies were collected from 10 healthy recreationally active participants before, immediately post, and 3h after a session of HIIE performed at the same absolute exercise intensity before and after HVT (Pre-HVT and Post-HVT, respectively). The protein content of common markers of exercise-induced mitochondrial biogenesis were assessed in nuclear- and cytosolic-enriched fractions by immunoblotting; mRNA contents of key transcription factors and mitochondrial genes were assessed by qPCR. Despite exercise-induced increases in PGC-1α, p53, and plant homeodomain finger-containing protein 20 (PHF20) protein content, the phosphorylation of p53 and acetyl-CoA carboxylase (p-p53Ser15 and p-ACCSer79, respectively), and PGC-1α mRNA Pre-HVT, no significant changes were observed Post-HVT. Forty sessions of twice-daily high-intensity interval training blunted all of the measured exercise-induced molecular events associated with mitochondrial biogenesis that were observed Pre-HVT. Future studies should determine if this loss relates to the decrease in relative exercise intensity, habituation to the same exercise stimulus, or a combination of both.

scholarly journals PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity

2010 ◽  
Vol 299 (2) ◽  
pp. E145-E161 ◽  
Author(s):  
Vitor A. Lira ◽  
Carley R. Benton ◽  
Zhen Yan ◽  
Arend Bonen
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Transgenic Mice ◽  
Mitochondrial Biogenesis ◽  
Therapeutic Potential ◽  
Fiber Type ◽  
Acid Oxidation ◽  
Physiological Limits ◽  
Exercise Induced

The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization. We provide an overview of 1) the role of PGC-1α in exercise-mediated muscle adaptation and 2) the possible insulin-sensitizing role of PGC-1α. To these ends, the following questions are addressed. 1) How is PGC-1α regulated, 2) what adaptations are indeed dependent on PGC-1α action, 3) is PGC-1α altered in insulin resistance, and 4) are PGC-1α-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator? In skeletal muscle, an orchestrated signaling network, including Ca2+-dependent pathways, reactive oxygen species (ROS), nitric oxide (NO), AMP-dependent protein kinase (AMPK), and p38 MAPK, is involved in the control of contractile protein expression, angiogenesis, mitochondrial biogenesis, and other adaptations. However, the p38γ MAPK/PGC-1α regulatory axis has been confirmed to be required for exercise-induced angiogenesis and mitochondrial biogenesis but not for fiber type transformation. With respect to a potential insulin-sensitizing role of PGC-1α, human studies on type 2 diabetes suggest that PGC-1α and its target genes are only modestly downregulated (≤34%). However, studies in PGC-1α-knockout or PGC-1α-transgenic mice have provided unexpected anomalies, which appear to suggest that PGC-1α does not have an insulin-sensitizing role. In contrast, a modest (∼25%) upregulation of PGC-1α, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle. Taken altogether, there is substantial evidence that the p38γ MAPK-PGC-1α regulatory axis is critical for exercise-induced metabolic adaptations in skeletal muscle, and strategies that upregulate PGC-1α, within physiological limits, have revealed its insulin-sensitizing effects.

scholarly journals Differential effects of vitamin C or protandim on skeletal muscle adaptation to exercise

2018 ◽  
Vol 125 (2) ◽  
pp. 661-671 ◽  
Author(s):  
Danielle R. Bruns ◽  
Sarah E. Ehrlicher ◽  
Shadi Khademi ◽  
Laurie M. Biela ◽  
Frederick F. Peelor ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin C ◽  
Aerobic Exercise ◽  
Mitochondrial Biogenesis ◽  
Redox Balance ◽  
Nuclear Factor ◽  
Oxidative Challenge ◽  
Endogenous Antioxidants ◽  
Exercise Induced ◽  
Endogenous Antioxidant

Maintaining proteostasis is a key mechanism for preserving cell function. Exercise-stimulated proteostasis is regulated, in part, by redox-sensitive signaling. Several studies suggest that supplementation with exogenous antioxidants blunts exercise-induced cellular adaptations, although this conclusion lacks consensus. Our group uses a fundamentally different approach to maintain redox balance by treatment with bioactive phytochemicals to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 and downstream endogenous antioxidant pathways. We hypothesized that vitamin C (VitC) would interfere with redox-sensitive proteostatic mechanisms in skeletal muscle, whereas phytochemical treatment would permit proteostatic maintenance. We measured protein and DNA synthesis in skeletal muscle from high-volume voluntary wheel-running rats. Whereas phytochemical treatment permitted mitochondrial and other proteostatic adaptations to exercise, VitC treatment did not. During an in vitro oxidative challenge, phytochemical treatment helped maintain proteostasis, including the mitochondrial fraction while VitC did not. Our findings support the conclusion that VitC can blunt some of the beneficial adaptations to exercise. We propose that regulation of endogenous antioxidants represents a novel approach to maintain redox balance while still permitting redox-sensitive proteostatic adaptations. NEW & NOTEWORTHY Whether vitamin C blocks aerobic exercise adaptions lacks consensus, perhaps because of approaches that only assess markers of mitochondrial biogenesis. By directly measuring mitochondrial biogenesis, we demonstrate that vitamin C blunts exercise-induced adaptations. Furthermore, we show that treatment with Protandim, a purported nuclear factor (erythroid-derived 2)-like 2 activator that upregulates endogenous antioxidants, permits mitochondrial biogenesis. We confirm that vitamin C blunts aerobic exercise adaptions, whereas Protandim does not, suggesting targeting the endogenous antioxidant network facilitates adaptations to exercise.

Looking beyond PGC-1α: emerging regulators of exercise-induced skeletal muscle mitochondrial biogenesis and their activation by dietary compounds

2020 ◽  
Vol 45 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Hashim Islam ◽  
David A. Hood ◽  
Brendon J. Gurd
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Respiratory Function ◽  
Human Skeletal Muscle ◽  
Ppar Gamma ◽  
Master Regulator ◽  
Mechanistic Insight ◽  
Simplistic Notion ◽  
Exercise Induced ◽  
Insight Into

Despite its widespread acceptance as the “master regulator” of mitochondrial biogenesis (i.e., the expansion of the mitochondrial reticulum), peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 alpha (PGC-1α) appears to be dispensable for the training-induced augmentation of skeletal muscle mitochondrial content and respiratory function. In fact, a number of regulatory proteins have emerged as important players in skeletal muscle mitochondrial biogenesis and many of these proteins share key attributes with PGC-1α. In an effort to move past the simplistic notion of a “master regulator” of mitochondrial biogenesis, we highlight the regulatory mechanisms by which nuclear factor erythroid 2-related factor 2 (Nrf2), estrogen-related receptor gamma (ERRγ), PPARβ, and leucine-rich pentatricopeptide repeat-containing protein (LRP130) may contribute to the control of skeletal muscle mitochondrial biogenesis. We also present evidence supporting/refuting the ability of sulforaphane, quercetin, and epicatechin to promote skeletal muscle mitochondrial biogenesis and their potential to augment mitochondrial training adaptations. Targeted activation of specific pathways by these compounds may allow for greater mechanistic insight into the molecular pathways controlling mitochondrial biogenesis in human skeletal muscle. Dietary activation of mitochondrial biogenesis may also be useful in clinical populations with basal reductions in mitochondrial protein content, enzyme activities, and/or respiratory function as well as individuals who exhibit a blunted skeletal muscle responsiveness to contractile activity. Novelty The existence of redundant pathways leading to mitochondrial biogenesis refutes the simplistic notion of a “master regulator” of mitochondrial biogenesis. Dietary activation of specific pathways may provide greater mechanistic insight into the exercise-induced mitochondrial biogenesis in human skeletal muscle.

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