Gene expression profiling in Chinese mininature pig liver tissue following clenbuterol administration
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE13786 | GEO | 2010/07/01
SECONDARY ACCESSION(S): PRJNA110617
REPOSITORIES: GEO
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Project description:Clenbuterol-HCL can greatly reduce fat deposition and increase skeletal muscle growth at high dosages. In order to advance our understanding of the fundamental molecular mechanisms, Genechips were used to study the differential gene expression profiles of liver tissues among the pigs with/without Clenbuterol-HCL. Differentially expressed genes identified will be the candidates for further investigations on the molecular mechanisms involved in Clenbuterol-HCL of exerting repartition effects on adipose and skeletal muscle tissue. 4 Chinese mininature pigs were broken into 2 groups with each group having two full sib pigs with the same gender. For the following 8 weeks, test pigs were fed 25 mg/kg clenbuterol twice daily in their diets for 4 weeks and 50 mg/kg clenbuterol for another 4 weeks. The vehicle control pigs were administered in the same manner except that no clenbuterol was added in their diets. The liver expression profiles of 4 pigs were analyzed using Porcine Genome GeneChip. After hybridization, genechips were washed and stained in the Affymetrix Fluidics Station 400 and scanned by using Hewlett-Packard GeneArray Scanner G2500A.
2010-07-30 | E-GEOD-13786 | biostudies-arrayexpress
Project description:Background: Beta-adrenergic receptor agonists (BA) induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. We chose to evaluate global changes in gene expression by utilizing the Affymetrix platform to identify gene expression changes in mouse skeletal muscle. Changes in gene expression were evaluated 24 h (1D) and 10 days (10D) after administration of the BA clenbuterol. Results: Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P < 0.01) and increased body weight gain (P < 0.05) 24 h or 10 d, respectively, after initiation of clenbuterol treatment. A total of 22,787 probesets were evaluated with 113 probesets defined as differentially expressed based on a false discovery rate of 10%. Differential mRNA abundance of four of these genes was validated in an independent experiment by quantitative PCR. Patterns of gene expression change observed from the microarray data suggested more genes are differentially regulated after 24 h than 10 d of BA administration. Functional characterization of differentially expressed genes revealed several categories that participate in biological processes important to skeletal muscle growth, including regulators of transcription and translation, mediators of cell-signaling pathways, and genes involved in polyamine metabolism. Included within these lists were several genes previously associated with myogenic differentiation, along with multiple genes known to promote a general up-regulation of translation. Conclusions: Global evaluation of gene expression after administration of clenbuterol identified changes gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in the mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on the proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Additionally, increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators, rather than a sustained up-regulation of gene expression at the transcriptional level. Additionally, numerous other genes and physiological pathways were identified that will be important targets for further investigations of the hypertrophic effect of BA on skeletal muscle. Keywords: Compound administration, time course
2006-03-18 | GSE4490 | GEO
Project description:Background: Beta-adrenergic receptor agonists (BA) induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. We chose to evaluate global changes in gene expression by utilizing the Affymetrix platform to identify gene expression changes in mouse skeletal muscle. Changes in gene expression were evaluated 24 h (1D) and 10 days (10D) after administration of the BA clenbuterol. Results: Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P < 0.01) and increased body weight gain (P < 0.05) 24 h or 10 d, respectively, after initiation of clenbuterol treatment. A total of 22,787 probesets were evaluated with 113 probesets defined as differentially expressed based on a false discovery rate of 10%. Differential mRNA abundance of four of these genes was validated in an independent experiment by quantitative PCR. Patterns of gene expression change observed from the microarray data suggested more genes are differentially regulated after 24 h than 10 d of BA administration. Functional characterization of differentially expressed genes revealed several categories that participate in biological processes important to skeletal muscle growth, including regulators of transcription and translation, mediators of cell-signaling pathways, and genes involved in polyamine metabolism. Included within these lists were several genes previously associated with myogenic differentiation, along with multiple genes known to promote a general up-regulation of translation. Conclusions: Global evaluation of gene expression after administration of clenbuterol identified changes gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in the mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on the proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Additionally, increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators, rather than a sustained up-regulation of gene expression at the transcriptional level. Additionally, numerous other genes and physiological pathways were identified that will be important targets for further investigations of the hypertrophic effect of BA on skeletal muscle. Experiment Overall Design: A total of 27 mice were used to represent three treatments. Hybridizations were done using RNA pools from 3 mice, with 3 pools (replicates) per treatment. Treatments included control, 1 day of clenbuterol administration, and 10 days of clenbuterol administration. Data represent skeletal muscle gene expression.
2008-06-13 | E-GEOD-4490 | biostudies-arrayexpress
Project description:Transcription profiling of skeletal muscle (tibialis anterior) of 5-week-old male wild type and myostatin null mice given ad libitum access to 20ppm clenbuterol hydrochloride in drinking water or plain tap water for 2 weeks. The objective of the study was to determine overlap in the mechanisms of muscle hypertrophy of the two models. 2x2 factorial arrangement of genotype (wild type and myostatin null) and clenbuterol treatment (control and clenbuterol at 20 ppm) with 4 replicates.
2014-02-03 | E-GEOD-27577 | biostudies-arrayexpress
Project description:Transcription profiling of skeletal muscle (tibialis anterior) of 5-week-old male wild type and myostatin null mice given ad libitum access to 20ppm clenbuterol hydrochloride in drinking water or plain tap water for 2 weeks. The objective of the study was to determine overlap in the mechanisms of muscle hypertrophy of the two models.
2014-02-03 | GSE27577 | GEO
Project description:Background Clenbuterol, a beta-agonist, can dramatically reduce pig adipose accumulation at high dosages. However, it has been banned in pig production because people who eat pig products treated with clenbuterol can be poisoned by the clenbuterol residues. To understand the molecular mechanism for this fat reduction, cDNA microarray, real-time PCR, two-dimensional electrophoresis and mass spectra were used to study the differential gene expression profiles of pig adipose tissues treated with/without clenbuterol. The objective of this research is to identify novel genes and physiological pathways that potentially facilitate clenbuterol induced reduction of adipose accumulation. Results Clenbuterol was found to improve the lean meat percentage about 10 percent (P< 0.5). The adipose cells became smaller and the muscle fibers became thicker with the administration of clenbuterol. The mRNA abundance of 82 genes (ESTs) were found to be statistically differentially expressed based on the Student t-test (P<0.5) in the microarray analyses which containing 3358 genes (ESTs).Theses 82 genes (ESTs) were divided into four groups according to their Gene Ontology Biological Process descriptions. 16 genes were cellular metabolism related genes (including five lipids metabolism related such as apolipoprotein D and apolipoprotein R), 10 were signal transduction related genes, 45 were expressed sequence tags (ESTs) and other 11 others were of various categories. Eleven of the 82 genes (ESTs) were chosen for real-time PCR analysis, with eight of them induced to express similar magnitudes as in the microarray analyses, two could not be detected and one expressed magnitudes that disagreed with the microarray results. Apolipoprotein R was also found to be up-regulated by the proteomic analysis. Conclusions Profound changes were observed in adipose cells after administration of clenbuterol in pigs by histological section and cDNA microarray techniques. The adipose cells became smaller with stimulation by clenbuterol. Changes in mRNA abundance indicated that DNA transcription and protein translation were enhanced in the adipose cells with clenbuterol stimulation. Five lipids metabolism related genes, such as apoD and apoR, were significantly up-regulated. ApoR was up-regulated in both the mRNA transcription and the protein synthesis. ApoR may be one of the critical molecules through which clenbuterol reduces fat accumulation. Keywords: dose response
2007-12-17 | GSE8093 | GEO
Project description:Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β<sub>2-</sub>adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β<sub>2</sub>-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β<sub>2</sub>-adrenergic receptors and the stimulatory G protein, G<sub>s</sub>. Unbiased transcriptomic and metabolomic analyses showed that chronic β<sub>2</sub>-adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β<sub>2</sub>-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.
2022-08-26 | MTBLS467 | MetaboLights
Project description:Background: Clenbuterol, a beta2-adrenergic receptor agonist, is used therapeutically to treat respiratory conditions in the horse. However, by virtue of its mechanism of action it has been suggested that clenbuterol may also have repartitioning affects in horses and as such the potential to affect performance. Clenbuterol decreases the percent fat and increases fat-free mass following high dose administration in combination with intense exercise in horses. In the current study, microarray analysis and real-time PCR were used to study the temporal effects of low and high dose chronic clenbuterol administration on differential gene expression of several skeletal muscle myosin heavy chains, genes involved in lipid metabolism and the β2-adrenergic receptor. The effect of clenbuterol administration on differential gene expression has not been previously reported in the horse, therefore the primary objective of the current study was to describe clenbuterol-induced temporal changes in gene expression following chronic oral administration of clenbuterol at both high and low doses. Steady state clenbuterol concentrations were achieved at approximately 50 hours post administration of the first dose for the low dose regimen and at approximately 18-19 days (10 days post administration of 3.2 μg/kg) for the escalating dosing regimen. Following chronic administration of the low dose (0.8 µg/kg BID) of clenbuterol, a total of 114 genes were differentially expressed, however, none of these changes were found to be significant following FDR adjustment of the p-values. A total of 7,093 genes were differentially expressed with 3,623 genes up regulated and 3,470 genes down regulated following chronic high dose administration. Of the genes selected for further study by real-time PCR, down-regulation of genes encoding myosin heavy chains 2 and 7, steroyl CoA desaturase and the β2-adrenergic receptor were noted. For most genes, expression levels returned towards baseline levels following cessation of drug administration. Conclusion: This study showed no evidence of modified gene expression following chronic low dose administration of clenbuterol to horses. However, following chronic administration of high doses of clenbuterol alterations were noted in transcripts encoding various myosin heavy chains, lipid metabolizing enzymes and the β2-adrenergic receptor.
2016-03-24 | GSE79559 | GEO
Project description:Background: Clenbuterol, a beta2-adrenergic receptor agonist, is used therapeutically to treat respiratory conditions in the horse. However, by virtue of its mechanism of action it has been suggested that clenbuterol may also have repartitioning affects in horses and as such the potential to affect performance. Clenbuterol decreases the percent fat and increases fat-free mass following high dose administration in combination with intense exercise in horses. In the current study, microarray analysis and real-time PCR were used to study the temporal effects of low and high dose chronic clenbuterol administration on differential gene expression of several skeletal muscle myosin heavy chains, genes involved in lipid metabolism and the β2-adrenergic receptor. The effect of clenbuterol administration on differential gene expression has not been previously reported in the horse, therefore the primary objective of the current study was to describe clenbuterol-induced temporal changes in gene expression following chronic oral administration of clenbuterol at both high and low doses. Steady state clenbuterol concentrations were achieved at approximately 50 hours post administration of the first dose for the low dose regimen and at approximately 18-19 days (10 days post administration of 3.2 μg/kg) for the escalating dosing regimen. Following chronic administration of the low dose (0.8 µg/kg BID) of clenbuterol, a total of 114 genes were differentially expressed, however, none of these changes were found to be significant following FDR adjustment of the p-values. A total of 7,093 genes were differentially expressed with 3,623 genes up regulated and 3,470 genes down regulated following chronic high dose administration. Of the genes selected for further study by real-time PCR, down-regulation of genes encoding myosin heavy chains 2 and 7, steroyl CoA desaturase and the β2-adrenergic receptor were noted. For most genes, expression levels returned towards baseline levels following cessation of drug administration. Conclusion: This study showed no evidence of modified gene expression following chronic low dose administration of clenbuterol to horses. However, following chronic administration of high doses of clenbuterol alterations were noted in transcripts encoding various myosin heavy chains, lipid metabolizing enzymes and the β2-adrenergic receptor. Five healthy horses were studied. Twenty-two of the horses received 0.8 µg/kg clenbuterol PO BID for 30 days and an additional 4 horses received 0.8 µg/kg, BID x 3 days; 1.6 µg/kg, BID x 3 days; 2.4 µg/kg, BID x 3 days; 3.2 µg/kg, BID for 21 days. Muscle biopsy samples were collected one day prior to administration of the first dose of clenbuterol and at a number of times post drug administration. A final sample was collected one-week post administration of the final dose (35 days post administration of the first dose). The tissue was transferred to a cryovial containing RNAlater (Qiagen Inc, Valencia, CA) and stored at -20° C until processed. Total RNA was purified using a miRNeasy Mini kit (RNeasy Mini, Qiagen Inc, Valencia, CA) and following the manufacturerâs instructions. Total RNA integrity was assessed using the Experion Automated Electrophoresis System (Bio-rad, Hercules, CA). Only RNA samples with RIN ⥠8 and 260/280 ratios between 1.7 and 2.1 were used. Equine specific microarrays (EquGene-1.0-st; Affymetrix, Santa Clara, CA), containing expression profiling of 30,559 well-characterized genes using 504,603 probes were utilized. To reduce biological noise as a result of genetic variability, each horse was analyzed separately and served as their own control for comparison of baseline samples to day 14 (low dose administration) or day 28 (escalating dose regimen). Five biological replicates per time point were tested. Purified total RNA (5 µg) was used for cDNA synthesis in accordance with the Ambion® WT Expression assay kit (Affymetrix, Santa Clara, CA) manufacturerâs protocol. In vitro transcription was used to incorporate biotin labels using the GeneChip® WT Terminal Labeling system (Affymetrix, Santa Clara, CA) and samples hybridized to the Equine microarray. Arrays were washed and stained on a Fluidics Station 450 (Affymetrix, Santa Clara, CA) and scanned on a GeneChip Scanner 3000 (Affymetrix, Santa Clara, CA) in accordance with manufacturerâs protocols. The microarrays were evaluated for differential gene expression using Transcriptome Analysis Console (TAC) and for hybridization quality control using Expression Console Software (Affymetrix, Santa Clara, CA). In brief, a total of five Cell Intensity Files were generated per time point, uploaded and normalized under the following conditions: PM (perfect match)-only as a PM intensity adjustment and the Robust Multichip Analysis (RMA) quantification method. For evaluation of the assays performance the number of differentially expressed genes detected between baseline and day 14 (low dose administration) or day 28 (escalating dose regimen) were assessed. Based on the TAC software userâs manual, genes with mean transformed ratios significantly less than -2 and larger than +2 were considered significantly regulated. A number of the significant genes were selected by filtering the genes using an ANOVA (p value < 0.05). A Pearson's correlation coefficient was used to calculate linear dependence between time point and baseline samples to evaluate the correlation coefficient, where 1 was a positive correlation and 0 was no correlation. For each probeset, expression at day 14 (low dose administration) or day 28 (escalating dose regimen) was compared to expression at baseline in the same horse using a paired t-test. Fold changes and their confidence intervals were calculated by exponentiating (base 2) the mean within-horse difference in expression for each gene and the associated t confidence intervals. P-values were adjusted for multiple testing using the False Discovery Rate (FDR) method. Analyses were conducted using the statistical software environment R, version 3.0.2 (R Core Team, 2013).
2016-03-24 | E-GEOD-79559 | biostudies-arrayexpress
Project description:Clenbuterol mediated changes in gene expression of mouse skeletal muscle
| PRJNA756795 | ENA