Pharmacological regulation of skeletal muscle gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11804 | GEO | 2008/06/18
SECONDARY ACCESSION(S): PRJNA109087
REPOSITORIES: GEO
Similar Datasets
Project description:Exercise activates serine/threonine kinase AMPK and transcriptional factor PPARdelta that re-model metabolism and endurance capacity of skeletal muscle. Whether and how synthetic activation of these molecules regulated muscle gene signature is unknown. We have conducted skeletal muscle microarrays from mice treated with AMPK agoinst (AICAR), PPARdelta agonist (GW1516) or the combination of the two drugs to investigate the individual and interactive effects of the two on muscle genes. Experiment Overall Design: C57Bl/6J mice were treated with Vehicle, AICAR, GW1516 and the combination of two drugs for 6 days, followed by collection of quadriceps for gene expression analysis.
2008-10-21 | E-GEOD-11804 | biostudies-arrayexpress
Project description:Exercise training increases endurance by inducing global gene expression changes in skeletal muscles. The extent to which the genetic effects of exercise can be mimicked by synthetic drugs is unknown. We measured global skeletal muscle expression in sedentary and exercised mice treated with vehicle or PPARdelta ligand GW1516. PPARdelta is a transcriptional regulator of muscle oxidative metabolism and fatigue resistance. Keywords: Pharmacology study
2008-06-18 | GSE11803 | GEO
Project description:Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging associated frailty may preclude physical activity. AMP-activated protein kinase (AMPK) is a transcriptional regulator important for muscle physiology. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (2-month-old), aged (23-month-old) C57Bl/6 mice, and transgenic mice with muscle-specific mutated AMPK alpha-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3 to 14 days and tested in the Morris water maze, rotarod and open field. Improved water maze performance and motor function was observed, albeit at longer duration of administration, in aged (14 days AICAR) than young (3 days AICAR) mice. In the AMPKDN mice, the compound did not enhance behavior, providing support for a muscle mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus genes relevant to neuronal development and plasticity were enriched. Altogether, endurance related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions. Key words: Skeletal Muscle, Brain, Exercise, AMPK, Learning and Memory, Morris water maze
2014-01-17 | GSE50873 | GEO
Project description:Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging associated frailty may preclude physical activity. AMP-activated protein kinase (AMPK) is a transcriptional regulator important for muscle physiology. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (2-month-old), aged (23-month-old) C57Bl/6 mice, and transgenic mice with muscle-specific mutated AMPK alpha-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3 to 14 days and tested in the Morris water maze, rotarod and open field. Improved water maze performance and motor function was observed, albeit at longer duration of administration, in aged (14 days AICAR) than young (3 days AICAR) mice. In the AMPKDN mice, the compound did not enhance behavior, providing support for a muscle mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus genes relevant to neuronal development and plasticity were enriched. Altogether, endurance related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions. Key words: Skeletal Muscle, Brain, Exercise, AMPK, Learning and Memory, Morris water maze 23-month old female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME) were housed under standard conditions, 3 mice per cage, with food and water ad libitum. Mice were injected intraperitoneally with 5-Aminoimidazole-4-carboxamide-1-a-D-ribofuranoside (AICAR, Toronto Research Chemicals Inc., Canada) dissolved in saline, 500 mg/kg/day for 3 (ACR3), 7 (ACR7) or 14 (ACR14) days or saline vehicle, for 3 (CTR) days. Thirty-three days after the final injection animals were deeply anesthetized with isofluorane and perfused transcardially with 0.9% NaCl solution. The gastrocnemius muscle and Hippocampus were quickly removed, frozen on dry ice and stored at M-bM-^HM-^R80 M-BM-0C for RNA isolation and microarray analysis.
2014-01-17 | E-GEOD-50873 | biostudies-arrayexpress
Project description:Exercise training increases endurance by inducing global gene expression changes in skeletal muscles. The extent to which the genetic effects of exercise can be mimicked by synthetic drugs is unknown. We measured global skeletal muscle expression in sedentary and exercised mice treated with vehicle or PPARdelta ligand GW1516. PPARdelta is a transcriptional regulator of muscle oxidative metabolism and fatigue resistance. Experiment Overall Design: Sedentary and exercise trained C57Bl/6J mice were treated with vehicle or GW1516 for 4 weeks, followed by collection of quadriceps for gene expression analysis.
2008-10-21 | E-GEOD-11803 | biostudies-arrayexpress
Project description:Skeletal muscle is a major contributor to whole-body glucose homeostasis and is an important endocrine organ. To date, few studies have undertaken the large-scale identification of skeletal muscle-derived secreted proteins (myokines), particularly in response to stimuli that activate pathways governing energy metabolism in health and disease. Whereas the AMP-activated protein kinase (AMPK) and insulin-signaling pathways have received notable attention for their ability to independently regulate skeletal muscle substrate metabolism, little work has examined their ability to re-pattern the secretome. The present study coupled the use of high-resolution MS-based proteomics and bioinformatics analysis of conditioned media derived from 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR – an AMPK activator)- and insulin-treated differentiated C2C12 myotubes. We quantified 858 secreted proteins, including cytokines and growth factors such as fibroblast growth factor-21 (Fgf21). We identified 377 and 118 proteins that were significantly altered by Insulin and AICAR treatment, respectively. Notably, the family of insulin growth factor binding-proteins (Igfbp) was differentially regulated by each treatment. Insulin- but not AICAR-induced conditioned media increased the mitochondrial respiratory capacity of myotubes, potentially via secreted factors. These findings may serve as an important resource to elucidate secondary metabolic effects of insulin and AICAR stimulation in skeletal muscle.
2021-09-15 | PXD025687 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE18583: Baseline skeletal muscle gene expression GSE35659: A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype (resting muscle after endurance training) Refer to individual Series
2012-02-10 | E-GEOD-35661 | biostudies-arrayexpress
Project description:AICAR is a metabolite with anti-tumoral properties. Its monophosphate derivative ZMP is an AMP mimetic activator of the protein kinases AMPK. However, AICAR also mediates AMPK-independent effects. A kinetic transcriptome analysis was therefore carried out in Ampkα1/α2 double knockout murine embryonic fibroblasts in response to AICAR in order to unveil these AMPK-independent functions,
2018-05-31 | GSE106460 | GEO
Project description:Physical activity promotes metabolic and cardiovascular health benefits that derive in part from the transcriptional responses to exercise that occur within skeletal muscle and other organs. There is interest in discovering a pharmacologic exercise mimetic that could imbue wellness and alleviate disease burden. However, the molecular physiology by which exercise signals the transcriptional response is highly complex, making it challenging to identify a single target for pharmacological mimicry. The current studies evaluated the transcriptome responses in skeletal muscle, heart, liver, and white and brown adipose to novel small molecule activators of AMPK (pan-activators for all AMPK isoforms) compared to that of exercise. A striking level of congruence between exercise and pharmacological AMPK activation was observed across the induced transcriptome of these five tissues. However, differences in acute metabolic response between exercise and pharmacologic AMPK activation were observed, notably for acute glycogen balances and related to the energy expenditure induced by exercise but not pharmacologic AMPK activation. Nevertheless, intervention with repeated daily administration of short-acting activation of AMPK was found to mitigate hyperglycemia and hyperinsulinemia in four rodent models of metabolic disease and without the cardiac glycogen accretion noted with sustained pharmacologic AMPK activation. These findings affirm that activation of AMPK is a key node governing exercise mediated transcription and is an attractive target as an exercise mimetic.
2019-02-27 | GSE92719 | GEO