scholarly journals Adult expression of PGC-1α and -1β in skeletal muscle is not required for endurance exercise-induced enhancement of exercise capacity

2016 ◽  
Vol 311 (6) ◽  
pp. E928-E938 ◽  
Author(s):  
Christopher Ballmann ◽  
Yawen Tang ◽  
Zachary Bush ◽  
Glenn C. Rowe
Keyword(s):  
Skeletal Muscle ◽  
Exercise Performance ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adult Skeletal Muscle ◽  
Training Response ◽  
Exercise Induced ◽  
Transport Complex ◽  
Specific Deletion

Exercise has been shown to be the best intervention in the treatment of many diseases. Many of the benefits of exercise are mediated by adaptions induced in skeletal muscle. The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family of transcriptional coactivators has emerged as being key mediators of the exercise response and is considered to be essential for many of the adaptions seen in skeletal muscle. However, the contribution of the PGC-1s in skeletal muscle has been evaluated by the use of either whole body or congenital skeletal muscle-specific deletion. In these models, PGC-1s were never present, thereby opening the possibility to developmental compensation. Therefore, we generated an inducible muscle-specific deletion of PGC-1α and -1β (iMyo-PGC-1DKO), in which both PGC-1α and -β can be deleted specifically in adult skeletal muscle. These iMyo-PGC-1DKO animals were used to assess the role of both PGC-1α and -1β in adult skeletal muscle and their contribution to the exercise training response. Untrained iMyo-PGC-1DKO animals exhibited a time-dependent decrease in exercise performance 8 wk postdeletion, similar to what was observed in the congenital muscle-specific PGC-1DKOs. However, after 4 wk of voluntary training, the iMyo-PGC-1DKOs exhibited an increase in exercise performance with a similar adaptive response compared with control animals. This increase was associated with an increase in electron transport complex (ETC) expression and activity in the absence of PGC-1α and -1β expression. Taken together these data suggest that PGC-1α and -1β expression are not required for training-induced exercise performance, highlighting the contribution of PGC-1-independent mechanisms.

scholarly journals The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 280 ◽  
Author(s):  
Anne-Marie Lundsgaard ◽  
Andreas M. Fritzen ◽  
Bente Kiens
Keyword(s):  
Skeletal Muscle ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Peroxisome Proliferator ◽  
Early Recovery ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Exercise ◽  
Exercise Induced

It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0–4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.

scholarly journals Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice

2017 ◽  
Vol 312 (5) ◽  
pp. E394-E406 ◽  
Author(s):  
Samuel Lee ◽  
Teresa C. Leone ◽  
Lisa Rogosa ◽  
John Rumsey ◽  
Julio Ayala ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Early Stage ◽  
Peroxisome Proliferator ◽  
Disuse Atrophy ◽  
Proof Of Concept ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Disuse ◽  
Training Response

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy.

scholarly journals Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle

2015 ◽  
Vol 308 (9) ◽  
pp. C710-C719 ◽  
Author(s):  
Anna Vainshtein ◽  
Liam D. Tryon ◽  
Marion Pauly ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Transmembrane Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipid Trafficking ◽  
Mitochondrial Transcription Factor ◽  
Energy Demands ◽  
Niemann Pick ◽  
Exercise Induced

Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α. Anna Vainshtein received the AJP-Cell 2015 Paper of the Year award. Listen to a podcast with Anna Vainshtein and coauthor David A. Hood at http://ajpcell.podbean.com/e/ajp-cell-paper-of-the-year-2015-award-podcast/ .

scholarly journals High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δAgonism

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Elisa Benetti ◽  
Raffaella Mastrocola ◽  
Mara Rogazzo ◽  
Fausto Chiazza ◽  
Manuela Aragno ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Gastrocnemius Muscle ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Intercellular Adhesion Molecule ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Intercellular Adhesion Molecule 1 ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome Proliferator Activated Receptor (PPAR)-δagonists may serve for treating metabolic diseases. However, the effects of PPAR-δagonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δagonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δupregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δactivation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.

Insulin resistance: cross-talk between adipose tissue and skeletal muscle, through free fatty acids, liver X receptor, and peroxisome proliferator-activated receptor-α signaling

2013 ◽  
Vol 15 (3) ◽  
Author(s):  
Ann Louise Olson
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Glucose Transporter ◽  
Control Point ◽  
Nuclear Hormone Receptor ◽  
Whole Body ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

AbstractSkeletal muscle and adipose tissue play a major role in the regulation of whole-body glucose homeostasis. Much of the coordinated regulation of whole-body glucose homeostasis results from the regulation of lipid storage and release by adipose tissue and efficient switching between glucose oxidation and fatty acid oxidation in skeletal muscle. A control point for these biochemical actions center around the regulation of the insulin responsive glucose transporter, GLUT4. This review examines the regulation of GLUT4 in adipose tissue and skeletal muscle, in the context of the steroid nuclear hormone receptor signaling.

scholarly journals Peroxisome Proliferator-Activated Receptor Delta: A Conserved Director of Lipid Homeostasis through Regulation of the Oxidative Capacity of Muscle

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Pieter de Lange ◽  
Assunta Lombardi ◽  
Elena Silvestri ◽  
Fernando Goglia ◽  
Antonia Lanni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Transcriptional Program ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisome Proliferator Activated Receptors ◽  
Metabolic Action

The peroxisome proliferator-activated receptors (PPARs), which are ligand-inducible transcription factors expressed in a variety of tissues, have been shown to perform key roles in lipid homeostasis. In physiological situations such as fasting and physical exercise, one PPAR subtype, PPARδ, triggers a transcriptional program in skeletal muscle leading to a switch in fuel usage from glucose/fatty acids to solely fatty acids, thereby drastically increasing its oxidative capacity. The metabolic action of PPARδ has also been verified in humans. In addition, it has become clear that the action of PPARδ is not restricted to skeletal muscle. Indeed, PPARδ has been shown to play a crucial role in whole-body lipid homeostasis as well as in insulin sensitivity, and it is active not only in skeletal muscle (as an activator of fat burning) but also in the liver (where it can activate glycolysis/lipogenesis, with the produced fat being oxidized in muscle) and in the adipose tissue (by incrementing lipolysis). The main aim of this review is to highlight the central role for activated PPARδ in the reversal of any tendency toward the development of insulin resistance.

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 Metabolic regulation of exercise-induced angiogenesis

2019 ◽  
Vol 1 (1) ◽  
pp. H1-H8 ◽  
Author(s):  
Tatiane Gorski ◽  
Katrien De Bock
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Metabolic Reprogramming ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Valuable Insight ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced

Skeletal muscle relies on an ingenious network of blood vessels, which ensures optimal oxygen and nutrient supply. An increase in muscle vascularization is an early adaptive event to exercise training, but the cellular and molecular mechanisms underlying exercise-induced blood vessel formation are not completely clear. In this review, we provide a concise overview on how exercise-induced alterations in muscle metabolism can evoke metabolic changes in endothelial cells (ECs) that drive muscle angiogenesis. In skeletal muscle, angiogenesis can occur via sprouting and splitting angiogenesis and is dependent on vascular endothelial growth factor (VEGF) signaling. In the resting muscle, VEGF levels are controlled by the estrogen-related receptor γ (ERRγ). Upon exercise, the transcriptional coactivator peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC1α) orchestrates several adaptations to endurance exercise within muscle fibers and simultaneously promotes transcriptional activation of Vegf expression and increased muscle capillary density. While ECs are highly glycolytic and change their metabolism during sprouting angiogenesis in development and disease, a similar role for EC metabolism in exercise-induced angiogenesis in skeletal muscle remains to be elucidated. Nonetheless, recent studies have illustrated the importance of endothelial hydrogen sulfide and sirtuin 1 (SIRT1) activity for exercise-induced angiogenesis, suggesting that EC metabolic reprogramming may be fundamental in this process. We hypothesize that the exercise-induced angiogenic response can also be modulated by metabolic crosstalk between muscle and the endothelium. Defining the underlying molecular mechanisms responsible for skeletal muscle angiogenesis in response to exercise will yield valuable insight into metabolic regulation as well as the determinants of exercise performance.

scholarly journals Adaptations to Post-exercise Cold Water Immersion: Friend, Foe, or Futile?

2021 ◽  
Vol 3 ◽  
Author(s):  
Mohammed Ihsan ◽  
Chris R. Abbiss ◽  
Robert Allan
Keyword(s):  
Exercise Performance ◽  
Cold Water ◽  
Water Immersion ◽  
Endurance Performance ◽  
Cold Water Immersion ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Exercise ◽  
Exercise Induced ◽  
Post Exercise Recovery

In the last decade, cold water immersion (CWI) has emerged as one of the most popular post-exercise recovery strategies utilized amongst athletes during training and competition. Following earlier research on the effects of CWI on the recovery of exercise performance and associated mechanisms, the recent focus has been on how CWI might influence adaptations to exercise. This line of enquiry stems from classical work demonstrating improved endurance and mitochondrial development in rodents exposed to repeated cold exposures. Moreover, there was strong rationale that CWI might enhance adaptations to exercise, given the discovery, and central role of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in both cold- and exercise-induced oxidative adaptations. Research on adaptations to post-exercise CWI have generally indicated a mode-dependant effect, where resistance training adaptations were diminished, whilst aerobic exercise performance seems unaffected but demonstrates premise for enhancement. However, the general suitability of CWI as a recovery modality has been the focus of considerable debate, primarily given the dampening effect on hypertrophy gains. In this mini-review, we highlight the key mechanisms surrounding CWI and endurance exercise adaptations, reiterating the potential for CWI to enhance endurance performance, with support from classical and contemporary works. This review also discusses the implications and insights (with regards to endurance and strength adaptations) gathered from recent studies examining the longer-term effects of CWI on training performance and recovery. Lastly, a periodized approach to recovery is proposed, where the use of CWI may be incorporated during competition or intensified training, whilst strategically avoiding periods following training focused on improving muscle strength or hypertrophy.

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