Dataset Information

Continuous infusion of 20-hydroxyecdysone increased mass of triceps brachii in C57BL/6 mice.

ABSTRACT: Phytoecdysteroids have been attributed with numerous pharmacological properties in animals, including increasing muscle mass, and 20-hydroxyecdysone (20E) is one of the most abundant phytoecdysteroids produced by plants. In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5?mg/kg/day) for 5 or 15?days using subcutaneously implanted Alzet® osmotic pumps. The masses of the total body, muscle groups and organs were determined. There was a significant increase (?p?=?0.01) in the mass of triceps brachii in mice treated with 20E for 5?days (115?±?8?mg) compared with mice treated with saline for 5?days (88?±?3?mg), however, there were no differences in the other measured parameters. To determine potential mechanisms of 20E in skeletal muscle, Illumina's Mouse Whole Genome-6 v2.0 Expression BeadChips were used to evaluate changes in gene expression of the triceps brachii after 20E infusion. Ingenuity Pathways Analysis was used to identify genes with the most evidence for differential expression, of which, 16 genes involved in the skeletal and muscular system were identified. Overall, the data suggest that 20E does not have potent anabolic properties, however, a muscle-specific increase was observed and genes were identified to provide an explanation for the muscle accretion.

SUBMITTER: Cheng DM

PROVIDER: S-EPMC3410052 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Continuous infusion of 20-hydroxyecdysone increased mass of triceps brachii in C57BL/6 mice.

Cheng Diana M DM Kutzler Louis W LW Boler Dustin D DD Drnevich Jenny J Killefer John J Lila Mary Ann MA

Phytotherapy research : PTR 20120412 1

Phytoecdysteroids have been attributed with numerous pharmacological properties in animals, including increasing muscle mass, and 20-hydroxyecdysone (20E) is one of the most abundant phytoecdysteroids produced by plants. In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 days using subcutaneously implanted Alzet® osmotic pumps. The masses of the total body, muscle groups and orga ...[more]

PMID: 22495969

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Project description:20-Hydroxyecdysone (20E) is the most abundant phytoecdysteroid produced by several plant families and has been attributed with numerous pharmacological properties in animals including anabolic and immune modulating effects. However, the in vivo bioactivity of phytoecdysteroids in mammals remains ambiguous, and moreover, the mechanism of action in mammals has yet to be determined. In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for five or fifteen days using subcutaneously implanted Alzet® osmotic pumps. The weights of the total body, muscle groups and organs were recorded and carcass composition was determined to evaluate changes in nutrient partitioning. There was a significant increase (p = 0.01) in the weight of triceps brachii in mice treated with 20E for five days (115 +/- 8 mg) compared to mice treated with saline for five days (88 +/- 3 mg), however, there were no differences in the other measured parameters. To determine potential mechanisms of action of 20E in skeletal muscle, Illumina’s Mouse Whole Genome-6 v2.0 Expression BeadChips were used to evaluate changes in gene expression after 20E infusion. False Discovery Rate correction of microarray data did not reveal any beadtypes that were differentially expressed. Therefore, Ingenuity Pathways Analysis (IPA) was used to identify genes with the most evidence for differential expression in the context of biological functions and pathways. IPA provided evidence for 20E involvement in processes including cellular growth and proliferation and cell-to-cell signaling and interaction. Overall, the data suggests that 20E does not have potent anabolic properties. IPA identified potential lead biological processes and pathways of 20E. Total RNA was extracted from the triceps brachii of C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 days using subcutaneously implanted Alzet® osmotic pumps to evaluate gene expression effects of 20E on mouse muscle.

Project description:Levels of myostatin expression and physical activity have both been associated with transcriptome dysregulation and skeletal muscle hypertrophy. The transcriptome of triceps brachii muscles from male C57/BL6 mice corresponding to two genotypes (wild-type and myostatin-reduced) under two conditions (high and low physical activity) was characterized using RNA-Seq. Synergistic and antagonistic interaction and ortholog modes of action of myostatin genotype and activity level on genes and gene pathways in this skeletal muscle were uncovered; 1,836, 238, and 399 genes exhibited significant (FDR-adjusted P-value < 0.005) activity-by-genotype interaction, genotype and activity effects, respectively. The most common differentially expressed profiles were (i) inactive myostatin-reduced relative to active and inactive wild-type, (ii) inactive myostatin-reduced and active wild-type, and (iii) inactive myostatin-reduced and inactive wild-type. Several remarkable genes and gene pathways were identified. The expression profile of nascent polypeptide-associated complex alpha subunit (Naca) supports a synergistic interaction between activity level and myostatin genotype, while Gremlin 2 (Grem2) displayed an antagonistic interaction. Comparison between activity levels revealed expression changes in genes encoding for structural proteins important for muscle function (including troponin, tropomyosin and myoglobin) and for fatty acid metabolism (some linked to diabetes and obesity, DNA-repair, stem cell renewal, and various forms of cancer). Conversely, comparison between genotype groups revealed changes in genes associated with G1-to-S-phase transition of the cell cycle of myoblasts and the expression of Grem2 proteins that modulate the cleavage of the myostatin propeptide. A number of myostatin-feedback regulated gene products that are primarily regulatory were uncovered, including microRNA impacting central functions and Piezo proteins that make cationic current-controlling mechanosensitive ion channels. These important findings extend hypotheses of myostatin and physical activity master regulation of genes and gene pathways, impacting medical practices and therapies associated with muscle atrophy in humans and companion animal species and genome-enabled selection practices applied to food-production animal species.

Dataset Information

Continuous infusion of 20-hydroxyecdysone increased mass of triceps brachii in C57BL/6 mice.

Publications

Continuous infusion of 20-hydroxyecdysone increased mass of triceps brachii in C57BL/6 mice.

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