Exercise and MEF2–HDAC interactions

2007 ◽  
Vol 32 (5) ◽  
pp. 852-856 ◽  
Author(s):  
Sean L. McGee
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Nuclear Export ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Positive Health ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase ◽  
Body Energy ◽  
Skeletal Muscle Adaptations

Exercise increases the metabolic capacity of skeletal muscle, which improves whole-body energy homeostasis and contributes to the positive health benefits of exercise. This is, in part, mediated by increases in the expression of a number of metabolic enzymes, regulated largely at the level of transcription. At a molecular level, many of these genes are regulated by the class II histone deacetylase (HDAC) family of transcriptional repressors, in particular HDAC5, through their interaction with myocyte enhancer factor 2 transcription factors. HDAC5 kinases, including 5′-AMP-activated protein kinase and protein kinase D, appear to regulate skeletal muscle metabolic gene transcription by inactivating HDAC5 and inducing HDAC5 nuclear export. These mechanisms appear to participate in exercise-induced gene expression and could be important for skeletal muscle adaptations to exercise.

scholarly journals Skeletal muscle AMP-activated protein kinase γ1H151R overexpression enhances whole body energy homeostasis and insulin sensitivity

2015 ◽  
Vol 309 (7) ◽  
pp. E679-E690 ◽  
Author(s):  
Milena Schönke ◽  
Martin G. Myers ◽  
Juleen R. Zierath ◽  
Marie Björnholm
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Transgenic Mice ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Α Subunit ◽  
Peripheral Tissues ◽  
Amp Activated Protein Kinase ◽  
Body Energy

AMP-activated protein kinase (AMPK) is a major sensor of energy homeostasis and stimulates ATP-generating processes such as lipid oxidation and glycolysis in peripheral tissues. The heterotrimeric enzyme consists of a catalytic α-subunit, a β-subunit that is important for enzyme activity, and a noncatalytic γ-subunit that binds AMP and activates the AMPK complex. We generated a skeletal muscle Cre-inducible transgenic mouse model expressing a mutant γ1-subunit (AMPKγ1H151R), resulting in chronic AMPK activation. The expression of the predominant AMPKγ3 isoform in skeletal muscle was reduced in extensor digitorum longus (EDL) muscle (81–83%) of AMPKγ1H151R transgenic mice, whereas the abundance and phosphorylation of the AMPK target acetyl-CoA carboxylase was increased in tibialis anterior muscle. Glycogen content was increased 10-fold in gastrocnemius muscle. Whole body carbohydrate oxidation was increased by 11%, and whereas glucose tolerance was unaffected, insulin sensitivity was increased in AMPKγ1H151R transgenic mice. Furthermore, perigonadal white adipose tissue mass and serum leptin were reduced in female AMPKγ1H151R transgenic mice by 38 and 51% respectively. Conversely, in male AMPKγ1H151R transgenic mice, food intake was increased (14%), but body weight and body composition were unaltered, presumably because of increased energy expenditure. In conclusion, transgenic activation of skeletal muscle AMPKγ1 in this model plays an important sex-specific role in skeletal muscle metabolism and whole body energy homeostasis.

scholarly journals The regulation and function of the NUAK family

2013 ◽  
Vol 51 (2) ◽  
pp. R15-R22 ◽  
Author(s):  
Xianglan Sun ◽  
Ling Gao ◽  
Hung-Yu Chien ◽  
Wan-Chun Li ◽  
Jiajun Zhao
Keyword(s):  
Protein Kinase ◽  
Structural Organization ◽  
Energy Homeostasis ◽  
Catalytic Domain ◽  
Whole Body ◽  
Upstream Kinase ◽  
Liver Kinase B1 ◽  
And Function ◽  
Amp Activated Protein Kinase ◽  
Body Energy

AMP-activated protein kinase (AMPK) is a critical regulator of cellular and whole-body energy homeostasis. Twelve AMPK-related kinases (ARKs; BRSK1, BRSK2, NUAK1, NUAK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4, and MELK) have been identified recently. These kinases show a similar structural organization, including an N-terminal catalytic domain, followed by a ubiquitin-associated domain and a C-terminal spacer sequence, which in some cases also contains a kinase-associated domain 1. Eleven of the ARKs are phosphorylated and activated by the master upstream kinase liver kinase B1. However, most of these ARKs are largely unknown, and the NUAK family seems to have different regulations and functions. This review contains a brief discussion of the NUAK family including the specific characteristics of NUAK1 and NUAK2.

Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans

2014 ◽  
Vol 307 (10) ◽  
pp. E885-E895 ◽  
Author(s):  
Marjolein A. Wijngaarden ◽  
Leontine E. H. Bakker ◽  
Gerard C. van der Zon ◽  
Peter A. C. 't Hoen ◽  
Ko Willems van Dijk ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Lipid Oxidation ◽  
Energy Homeostasis ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Protein Kinase Activity ◽  
Short Term ◽  
Muscle Energy

During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

Oral glucose ingestion attenuates exercise-induced activation of 5′-AMP-activated protein kinase in human skeletal muscle

2006 ◽  
Vol 342 (3) ◽  
pp. 949-955 ◽  
Author(s):  
Thorbjorn C.A. Akerstrom ◽  
Jesper B. Birk ◽  
Ditte K. Klein ◽  
Christian Erikstrup ◽  
Peter Plomgaard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Human Skeletal Muscle ◽  
Oral Glucose ◽  
Glucose Ingestion ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase

PIKfyve: a new fish in the growing pool of AMPK substrates

2013 ◽  
Vol 455 (2) ◽  
pp. e1-e3
Author(s):  
James S. V. Lally ◽  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Muscle Contractions ◽  
Whole Body ◽  
Glucose Homoeostasis ◽  
Increase Glucose Uptake ◽  
Biochemical Journal ◽  
Complex Events ◽  
Amp Activated Protein Kinase

Skeletal muscle is critical for whole-body glucose homoeostasis. Insulin and muscle contractions induced by exercise can increase glucose uptake through distinct intracellular signalling pathways involving PKB (protein kinase B)/Akt and AMPK (AMP-activated protein kinase) respectively. Whereas the proximal events governing these processes are becoming well understood, less is known about the regulation of the complex events necessary for the control of glucose uptake at the plasma membrane. In recent years, a number of common targets of AMPK and PKB/Akt have emerged as important components controlling glucose uptake, but the necessary phosphorylation events required for the control of glucose uptake have remained more elusive. In the current issue of the Biochemical Journal, Liu et al. identify that PIKfyve, a phosphoinositide phosphate kinase, is required for contraction-stimulated glucose uptake. They demonstrate that AMPK directly phosphorylates PIKfyve at Ser307, the same site as PKB/Akt, and that phosphorylation is increased in response to muscle contractions. These data provide compelling evidence for a new AMPK substrate that converges with PKB/Akt signalling and may be critical for the control of glucose uptake in skeletal muscle.

AMP-activated protein kinase and the regulation of glucose transport

2006 ◽  
Vol 291 (5) ◽  
pp. E867-E877 ◽  
Author(s):  
Nobuharu Fujii ◽  
Niels Jessen ◽  
Laurie J. Goodyear
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Cardiac Muscle ◽  
Glucose Transport ◽  
Whole Body ◽  
Insulin Resistant ◽  
Treatment And Prevention ◽  
Ampk Activity ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated by acute increases in the cellular [AMP]/[ATP] ratio. In skeletal and/or cardiac muscle, AMPK activity is increased by stimuli such as exercise, hypoxia, ischemia, and osmotic stress. There are many lines of evidence that increasing AMPK activity in skeletal muscle results in increased rates of glucose transport. Although similar to the effects of insulin to increase glucose transport in muscle, it is clear that the underlying mechanisms for AMPK-mediated glucose transport involve proximal signals that are distinct from that of insulin. Here, we discuss the evidence for AMPK regulation of glucose transport in skeletal and cardiac muscle and describe research investigating putative signaling mechanisms mediating this effect. We also discuss evidence that AMPK may play a role in enhancing muscle and whole body insulin sensitivity for glucose transport under conditions such as exercise, as well as the use of the AMPK activator AICAR to reverse insulin-resistant conditions. The identification of AMPK as a novel glucose transport mediator in skeletal muscle is providing important insights for the treatment and prevention of type 2 diabetes.

The role of AMP-activated protein kinase in the coordination of skeletal muscle turnover and energy homeostasis

2012 ◽  
Vol 303 (5) ◽  
pp. C475-C485 ◽  
Author(s):  
Anthony M. J. Sanchez ◽  
Robin B. Candau ◽  
Alfredo Csibi ◽  
Allan F. Pagano ◽  
Audrey Raibon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Energy Status ◽  
Muscle Plasticity ◽  
Glucose And Lipid Metabolism ◽  
Muscle Homeostasis ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that acts as a sensor of cellular energy status switch regulating several systems including glucose and lipid metabolism. Recently, AMPK has been implicated in the control of skeletal muscle mass by decreasing mTORC1 activity and increasing protein degradation through regulation of ubiquitin-proteasome and autophagy pathways. In this review, we give an overview of the central role of AMPK in the control of skeletal muscle plasticity. We detail particularly its implication in the control of the hypertrophic and atrophic signaling pathways. In the light of these cumulative and attractive results, AMPK appears as a key player in regulating muscle homeostasis and the modulation of its activity may constitute a therapeutic potential in treating muscle wasting syndromes in humans.

scholarly journals Role of Adenosine 5′-Monophosphate-Activated Protein Kinase in Interleukin-6 Release from Isolated Mouse Skeletal Muscle

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 600-606 ◽  
Author(s):  
Stephan Glund ◽  
Jonas T. Treebak ◽  
Yun Chau Long ◽  
Romain Barres ◽  
Benoit Viollet ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Extensor Digitorum Longus ◽  
Protein Release ◽  
Extensor Digitorum ◽  
Whole Body ◽  
Wild Type ◽  
Amp Activated Protein Kinase ◽  
Respective Wild Type

IL-6 is released from skeletal muscle during exercise and has consequently been implicated to mediate beneficial effects on whole-body metabolism. Using 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), a pharmacological activator of 5′-AMP-activated protein kinase (AMPK), we tested the hypothesis that AMPK modulates IL-6 release from isolated muscle. Skeletal muscle from AMPKα2 kinase-dead transgenic, AMPKα1 knockout (KO) and AMPKγ3 KO mice and respective wild-type littermates was incubated in vitro, in the absence or presence of 2 mmol/liter AICAR. Skeletal muscle from wild-type mice was also incubated with the AMPK activator A-769662. Incubation of mouse glycolytic extensor digitorum longus and oxidative soleus muscle for 2 h was associated with profound IL-6 mRNA production and protein release, which was suppressed by AICAR (P < 0.001). Basal IL-6 release from soleus was increased between AMPKα2 kinase-dead and AMPKα1 KO and their respective wild-type littermates (P < 0.05), suggesting AMPK participates in the regulation of IL-6 release from oxidative muscle. The effect of AICAR on muscle IL-6 release was similar between AMPKα2 KD, AMPKα1 KO, and AMPKγ3 KO mice and their respective wild-type littermates (P < 0.001), indicating AICAR-mediated suppression of IL-6 mRNA expression and protein release is independent of AMPK function. However, IL-6 release from soleus, but not extensor digitorum longus, was reduced 45% by A-769662. Our results on basal and A-769662-mediated IL-6 release provide evidence for a role of AMPK in the regulation of IL-6 release from oxidative skeletal muscle. Furthermore, in addition to activating AMPK, AICAR suppresses IL-6 release by an unknown, AMPK-independent mechanism. Using transgenic and knockout mouse models to perturb AMP-activated protein kinase (AMPK) signaling, we provide evidence that AMPK-dependent pathways regulate IL-6 release from isolated oxidative skeletal muscle.

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