Unknown,Transcriptomics,Genomics,Proteomics

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Effects of dexamethasone on human skeletal muscle and adipose tissue

ABSTRACT: Context: Glucocorticoids are frequently prescribed drugs with important side-effects such as glucose intolerance and tissue remodelling. Objective: The goal was to explore the molecular basis of the crosstalk between adipose tissue and skeletal muscle during short term glucocorticoid treatment. Design and Intervention: Healthy male subjects were assigned to a 4-d treatment with dexamethasone at 4mg/d. Main Outcome Measures: Primary outcome measures were gene expression profiling of adipose tissue and skeletal muscle. Urinary cortisol and metabolic biochemistry were also assessed. Dexamethasone was provided in 0.5 mg tablets as 4mg per day during 4 days to male healthy volunteers. Skeletal muscle and adipose tissue biopsies were obtained at the beginning and at the end of the protocol. The transcriptome analysis compared before vs. after the 4 days dexamethasone treatment using a dye swap design and whole genome 4x44k oligonucleotide arrays (Agilent Technologies).

ORGANISM(S): Homo sapiens

SUBMITTER: Nathalie Viguerie

PROVIDER: E-GEOD-17992 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue.

Viguerie Nathalie N Picard Flora F Hul Gabby G Roussel Balbine B Barbe Pierre P Iacovoni Jason S JS Valle Carine C Langin Dominique D Saris Wim H M WH

Physiological genomics 20111122 2

Glucocorticoids are frequently prescribed drugs with important side-effects such as glucose intolerance and tissue remodeling. The goal was to explore the molecular basis of the response of skeletal muscle and adipose tissue during a short-term dexamethasone treatment to better understand the induction of side-effects of glucocorticoids on these metabolic tissues. Fifteen healthy male subjects were assigned to a 4-day treatment with dexamethasone at 4 mg/day. The primary outcome measures were ch ...[more]

PMID: 22108209

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Project description:Objective: This work aimed at identifying and characterizing differences in subcutaneous adipose tissue (SAT) gene expression patterns between subjects succeeding weight control against subjects regaining weight 6 months after a low calorie diet program. Methods: Weight-reduced obese subjects from 8 European countries were randomized into 4 diets differing in protein and glycemic index. In addition to the anthropometric and plasma parameters, SAT biopsies were taken at the beginning (CID2) and the end (CID3) of the weight maintenance intervention. Pan-genomic cDNA microarrays were used to define SAT gene expression profiles at both CID2 and CID3 of 22 subjects succeeding weight maintenance (successful subjects; mean weight change= -2.6 ± 1.2 kg) and 22 subjects regaining weight (unsuccessful subjects; mean weight change= 3.9 ± 1.3 kg) among the 4 dietary arms. Results: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather to differences in diet macronutrient composition. An ANCOVA analysis with total energy intake at CID3 as covariant led us to the definition of 1339 differential genes. Functional analysis of differential genes showed that cellular growth and proliferation, inflammation, cell death, cancer, cellular function and maintenance were the main biological processes involving these differential genes. Overall design: SAT transcriptome was defined at the beginning (CID2) and at the end (CID3) of the dietary intervention program using a common reference design: Cyanine-5 dye was incorporated into all SAT samples, while a reference RNA pool made of the mix of commercial human liver, adipose tissue, and skeletal muscle RNA was labeled with cyanine-3 dye. Samples were hybridized to Agilent 44K whole human genome microarrays. Evolution in gene expression patterns after dietary intervention was tested in terms of the ratio after/before dietary intervention (CID3/CID2) ratio.

Project description:Context: Exercise training is a plausible model for identification of molecular mechanisms that cause metabolic-related changes in human skeletal muscle. Objective: The goal was to explore the molecular basis of the adaptation of skeletal muscle to exercise training. Design and Intervention: Obese male subjects were subjected to an individualized supervised training program targeted in order to optimize lipid oxidation during 8 weeks. Main Outcome Measures: Primary outcome measures were gene expression profiling of skeletal muscle. Body composition, oral glucose tolerance test, Resting metabolic rate, respiratory quotient, maximal oxygen uptake and metabolic biochemistry were also assessed. Overall Design The obese (BMI 30-36) male volunteers (age 32-42) were asked to refrain from vigorous physical activity 48h before presenting to the clinical investigation centre, and ate a weight-maintaining diet consisting of 35% fat, 16% protein, and 49% carbohydrates two days before the experiment. Muscle biopsies of Vastus Lateralis weighing 60–100 mg were obtained using the Bergstrom technique, cleaned and snap-frozen in liquid nitrogen. Resting metabolic rate, respiratory quotient and maximal oxygen uptake were assessed. The subjects were investigated at baseline and after 8 weeks of supervised aerobic exercise training program consisting of daily sessions of 45-60 min of endurance exercise, 5 days a week, at least 48-72h after the last acute exercise bout. Skeletal muscle biopsies were obtained at the beginning and at the end of the protocol. Transcriptome analysis compared 8 subjects before vs. after training using arrays using a common reference design (Cy5 dye was incorporated into all muscle RNA samples, while a reference RNA pool made of the mix of commercial human liver, adipose tissue and skeletal muscle RNA was labelled with Cy3 dye (Applied Biosystems/Ambion, Foster City, USA)( and whole genome 4x44k oligonucleotide arrays (Agilent Technologies).

Project description:In multiple sclerosis (MS) and experimental models of demyelination, myelin repair is mostly achieved by oligodendrocyte precursor cells (OPCs). To gain insight into the biological specificity of these adult precursors, in the perspective to better understand why remyelination often fails in MS, we performed a micro-array analysis on purified populations of murine OPCs and oligodendrocytes. We demonstrated that, in a control environment, M-bM-^@M-^\quiescentM-bM-^@M-^] adult OPCs are more mature than neonatal OPCs, with a mRNA profile closer to oligodendrocytes. However, when demyelination occurs, adult OPCs revert to an immature gene expression profile, acquiring higher migration and faster differentiation capacities. Among the many genes differentially regulated by these M-bM-^@M-^\activatedM-bM-^@M-^] adult OPCs, genes of the innate immune response, IL1M-NM-2 and CCL2 were strongly upregulated after demyelination, with increased protein expression in experimental demyelinating lesions and within MS plaques. We first showed in vitro that both IL1M-NM-2 and CCL2 M-bM-^@M-^\accountM-bM-^@M-^] for increased migration capacities of adult OPCs, an effect that is suppressed by corresponding receptor blockade. Focusing on Ccl2, we then demonstrated that lentiviral over-expression of Ccl2 increases motility of M-bM-^@M-^\quiescentM-bM-^@M-^] adult OPCs, which become as mobile as M-bM-^@M-^\activatedM-bM-^@M-^] adult OPCs. This in vitro gain of function was further confirmed in vivo, by showing an increased migration of grafted CG4 oligodendroglial cells over-expressing-Ccl2. These results, demonstrating that M-bM-^@M-^\activatedM-bM-^@M-^] adult OPCs upregulate immune cues favouring their migration, open new perspective of demyelination-induced immune-glial interactions, which might influence both oligodendroglial and inflammatory cells, therefore play a key role in lesion fate in multiple sclerosis. In this study, we loaded purified population of progenitors of oligodendrocytes (OPCs) (from neonatal, 2-month-old, 2-month-old and cuprizone-treated brains) and of mature oligodendrocytes (OLs) (2-month-old brains) and compared their gene expression. We compared gene expression of neonatal OPCs, adult OPCs, adult OLs and adult OPCs from control conditions and from demyelinating conditions, using 3 to 4 independant replicates in each group.

Dataset Information

Effects of dexamethasone on human skeletal muscle and adipose tissue

Publications

Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue.

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