The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defense in skeletal muscles
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE73572 | GEO | 2015/12/16
SECONDARY ACCESSION(S): PRJNA297347
REPOSITORIES: GEO
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Project description:Transcriptional microarray analysis was conducted on gastrocnemius muscle of control and PGC-1β(i)skm-/- mice one week after the last tamoxifen administration using the Affymetrix Mouse Gene 1.0 ST. each sample represent a pool of 3 different mice.
2015-12-16 | E-GEOD-73572 | biostudies-arrayexpress
Project description:The transcriptional coregulators PGC-1α and PGC-1β modulate the expression of numerous partially overlapping genes involved in mitochondrial biogenesis and energetic metabolism. The physiological role of PGC-1β is poorly understood in skeletal muscle, a tissue of high mitochondrial content to produce ATP levels required for sustained contractions. Here we determine the physiological role of PGC-1β in skeletal muscle using mice, in which PGC-1β is selectively ablated in skeletal myofibres at adulthood (PGC-1β((i)skm-/-) mice). We show that myofibre myosin heavy chain composition and mitochondrial number, muscle strength and glucose homeostasis are unaffected in PGC-1β((i)skm-/-) mice. However, decreased expression of genes controlling mitochondrial protein import, translational machinery and energy metabolism in PGC-1β((i)skm-/-) muscles leads to mitochondrial structural and functional abnormalities, impaired muscle oxidative capacity and reduced exercise performance. Moreover, enhanced free-radical leak and reduced expression of the mitochondrial anti-oxidant enzyme Sod2 increase muscle oxidative stress. PGC-1β is therefore instrumental for skeletal muscles to cope with high energetic demands.
| S-EPMC4703903 | biostudies-literature
Project description:Peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) is a transcriptional regulator whose increased expression activates energy expenditure-related genes in skeletal muscles. However, how PGC-1β is regulated remains largely unclear. Here, we show that PGC-1β gene expression is negatively correlated with the expression of a transcription factor, forkhead box protein O1 (FOXO1), whose expression is increased during muscle atrophy. In the skeletal muscles of FOXO1-overexpressing transgenic mice, PGC-1β gene expression is decreased. Denervation or plaster cast-based unloading, as well as fasting, increases endogenous FOXO1 expression in skeletal muscles, with decreased PGC-1β expression. In the skeletal muscles of FOXO1-knockout mice, the decrease in PGC-1β expression caused by fasting was attenuated. Tamoxifen-inducible FOXO1 activation in C2C12 myoblasts causes a marked decrease of PGC-1β expression. These findings together reveal that FOXO1 activation suppresses PGC-1β expression. During atrophy with FOXO1 activation, decreased PGC-1β may decrease energy expenditure and avoid wasting energy.
| S-EPMC7327905 | biostudies-literature
Project description:In the present study we have studied the mechanistic and functional aspects of NCoR1 function in mouse skeletal muscle. NCoR1 muscle-specific knockout mice exhibited an increased oxidative metabolism. Global gene expression analysis revealed a high overlap between the effects of NCoR1 deletion and peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) overexpression on oxidative metabolism in skeletal muscle. The repressive effect of NCoR1 on oxidative phosphorylation gene expression specifically antagonizes PGC-1alpha-mediated coactivation of ERRalpha. We therefore delineated the molecular mechanism by which a transcriptional network controlled by corepressor and coactivator proteins determines the metabolic properties of skeletal muscle, thus representing a potential therapeutic target for metabolic diseases. Gene expression of a total of 20 gastrocnemius samples from control (CON, n = 5), NCoR1 muscle-specific knockout (NCoR1 MKO, n = 5), wild type (WT, n = 5) and PGC-1alpha muscle-specific transgenic (PGC-1alpha mTg, n = 5) adult male mice was analyzed using GeneChip® Gene 1.0 ST Array System (Affymetrix). NCoR1 MKO and PGC-1alpha mTg samples were compared to CON and WT samples, respectively.
2013-01-08 | E-GEOD-40439 | biostudies-arrayexpress
Project description:The fine-tuning of liver metabolism is essential to maintain the whole-body homeostasis and to prevent the onset of diseases. The peroxisome proliferator-activated receptor-γ coactivators (PGC-1s) are transcriptional key players of liver metabolism, able to regulate mitochondrial function, gluconeogenesis and lipid metabolism. Their activity is accurately modulated by post-translational modifications. Here, we showed that specific PGC-1s expression can lead to the upregulation of different microRNAs widely implicated in liver physiology and diseases development and progression, thus offering a new layer of complexity in the control of hepatic metabolism.
2019-12-14 | GSE142026 | GEO
Project description:The fine-tuning of liver metabolism is essential to maintain the whole-body homeostasis and to prevent the onset of diseases. The peroxisome proliferator-activated receptor-γ coactivators (PGC-1s) are transcriptional key players of liver metabolism, able to regulate mitochondrial function, gluconeogenesis and lipid metabolism. Their activity is accurately modulated by post-translational modifications. Here, we showed that specific PGC-1s expression can lead to the upregulation of different microRNAs widely implicated in liver physiology and diseases development and progression, thus offering a new layer of complexity in the control of hepatic metabolism.
2019-12-14 | GSE142027 | GEO
Project description:Title: Total Skeletal Muscle PGC-1 Deficiency Uncouples Mitochondrial Derangements from Fiber Type Determination and Insulin Sensitivity Abstract: Evidence is emerging that the PGC-1 coactivators serve a critical role in skeletal muscle metabolism, function, and disease. Mice with total PGC-1 deficiency in skeletal muscle (PGC-1α-/- βf/f/MLC-Cre mice) were generated and characterized. PGC-1α-/-βf/f/MLC-Cre mice exhibit a dramatic reduction in exercise performance compared to single PGC-1α- or PGC-1β-deficient mice and wild-type controls. The exercise phenotype of the PGC-1α-/-βf/f/MLC-Cre mice was associated with a marked diminution in muscle oxidative capacity and mitochondrial structural derangements consistent with fusion/fission and biogenic defects together with rapid depletion of muscle glycogen stores during exercise. Surprisingly, the skeletal muscle fiber type profile of the PGC-1α-/-βf/f/MLCCre mice was not significantly different than the wild-type mice. Moreover, insulin sensitivity and glucose tolerance were also not altered in the PGC-1α-/-βf/f/MLC-Cre mice. Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity. RNA from PGC-1alpha-/- beta f/f/Mlc1fcre was obtained and gene expression pattern compared with PGC-1alpha -/-, PGC-1beta f/f, and PGC-1beta f/f/Mlc1fCre controls. Results file descriptions: 1. GSE23365_skfloxAKO_PPexcl_genesup_GEO-8-16-2010: This table contains genes that were upregulated ≥2.0 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names. 2. GSE23365_skfloxAKO_PPexcl_genesdown_GEO-8-16-2010 This table contains genes that were downregulated ≤0.7 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names.
2010-12-01 | E-GEOD-23365 | biostudies-arrayexpress
Project description:Analysis of metabolic pathway gene expression. The hypothesis tested in the present study is to assess mRNA level changes in metabolic genes in enterocytes from intestine specific PGC-1β konckout mice. Total RNA obtained from ileum samples from IKOPGC-1β mice was compared to the total RNA extracted from their wild-type littermates.
2015-03-01 | E-GEOD-61640 | biostudies-arrayexpress
Project description:Analysis of metabolic pathway gene expression. The hypothesis tested in the present study is to assess mRNA level changes in metabolic genes in enterocytes from intestine specific PGC-1β konckout mice.
2015-03-01 | GSE61640 | GEO
Project description:To investigate age-related changes in muscle mitochondrial proteostasis, as well as the effect of higher and lower levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in this paradigm, we isolated RNA from M. gastrocnemius muscle tissue of muscle-specific PGC-1α gain- and loss-of-function mouse models, at the ages of three and twenty four months.
2023-08-04 | GSE233485 | GEO