Dataset Information

Genomic and lipidomic actions of nandrolone on detached rotator cuff muscle in sheep

ABSTRACT: Reversal of fatty infiltration of pennate rotator cuff muscle after tendon release is hitherto impossible. The administration of nandrolone starting at the time of tendon release prevents the increase in fat content, but does not revert established fatty infiltration. We hypothesised that tendon release and myotendinous retraction cause alterations in lipid related gene expression leading to fatty muscle infiltration, which can be suppressed by nandrolone through its genomic actions if applied immediately after tendon release. The effects of infraspinatus tendon release and subsequent tendon repair at 16 weeks were studied in six Swiss Alpine sheep. In the interventional groups, 150mg nandrolone was administered weekly after tendon release until sacrifice (N22W, n=6) or starting at the time of repair (N6W, n=6). Infraspinatus volume, composition, expressed transcripts, lipids, and selected proteins were analyzed at baseline, 16 and 22 weeks. Tendon release reduced infraspinatus volume by 22% and increased fat content from 11% to 38%. These changes were not affected by repair. Fatty infiltration was associated with up-regulation of 227 lipid species, and increased levels of the adipocyte differentiation marker PPARG2 (peroxisome proliferator-activated receptor gamma 2). Nandrolone abrogated lipid accumulation, halved the loss in fiber area percentage, and up-regulated androgen receptor levels and transcript expression in the N22W but not the N6W group. The results document that nandrolone mitigates muscle-to-fat transformation after tendon release via a general down-regulation of lipid accumulation concomitantly with up-regulated expression of its nuclear receptor and downstream transcripts in skeletal muscle. Reduced responsiveness of retracted muscle to nandrolone as observed in the N6W group is reflected by a down-regulated transcript response.

OTHER RELATED OMICS DATASETS IN: PXD009709

INSTRUMENT(S): SYNAPT G2 HDMS (Waters)

SUBMITTER: Martin FlÃ¼ck

PROVIDER: MTBLS322 | MetaboLights | 2017-07-14

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS322	Other
	FILES	Other
	a_MTBLS322_metabolite_profiling_mass_spectrometry.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS322_metabolite_profiling_mass_spectrometry_v2_maf.tsv	Tabular

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Publications

Genomic and lipidomic actions of nandrolone on detached rotator cuff muscle in sheep.

Flück Martin M Ruoss Severin S Möhl Christoph B CB Valdivieso Paola P Benn Mario C MC von Rechenberg Brigitte B Laczko Endre E Hu Junmin J Wieser Karl K Meyer Dominik C DC Gerber Christian C

The Journal of steroid biochemistry and molecular biology 20160812 Pt B

Reversal of fatty infiltration of pennate rotator cuff muscle after tendon release is hitherto impossible. The administration of nandrolone starting at the time of tendon release prevents the increase in fat content, but does not revert established fatty infiltration. We hypothesised that tendon release and myotendinous retraction cause alterations in lipid related gene expression leading to fatty muscle infiltration, which can be suppressed by nandrolone through its genomic actions if applied i ...[more]

PMID: 27523963

Similar Datasets

Project description:This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS322 Abstract:Reversal of fatty infiltration of pennate rotator cuff muscle after tendon release is hitherto impossible. The administration of nandrolone starting at the time of tendon release prevents the increase in fat content, but does not revert established fatty infiltration. We hypothesised that tendon release and myotendinous retraction cause alterations in lipid related gene expression leading to fatty muscle infiltration, which can be suppressed by nandrolone through its genomic actions if applied immediately after tendon release. The effects of infraspinatus tendon release and subsequent tendon repair at 16 weeks were studied in six Swiss Alpine sheep. In the interventional groups, 150mg nandrolone was administered weekly after tendon release until sacrifice (N22W, n=6) or starting at the time of repair (N6W, n=6). Infraspinatus volume, composition, expressed transcripts, lipids, and selected proteins were analyzed at baseline, 16 and 22 weeks. Tendon release reduced infraspinatus volume by 22% and increased fat content from 11% to 38%. These changes were not affected by repair. Fatty infiltration was associated with up-regulation of 227 lipid species, and increased levels of the adipocyte differentiation marker PPARG2 (peroxisome proliferator-activated receptor gamma 2). Nandrolone abrogated lipid accumulation, halved the loss in fiber area percentage, and up-regulated androgen receptor levels and transcript expression in the N22W but not the N6W group. The results document that nandrolone mitigates muscle-to-fat transformation after tendon release via a general down-regulation of lipid accumulation concomitantly with up-regulated expression of its nuclear receptor and downstream transcripts in skeletal muscle. Reduced responsiveness of retracted muscle to nandrolone as observed in the N6W group is reflected by a down-regulated transcript response.

Project description:Identification and validation of the pathways and functions regulated by the orphan nuclear receptor, ROR alpha1, in skeletal muscle The retinoic acid receptor-related orphan receptor (ROR) alpha has been demonstrated to regulate lipid metabolism. We were interested in the physiologically relevant roles, and pathways regulated by RORalpha1 action in skeletal muscle. This major mass organ accounts for ~40% of the total body mass, and significant levels of lipid catabolism, glucose disposal and energy expenditure. We utilized the strategy of targeted muscle specific expression of a truncated (dominant negative) RORalphaâDE in transgenic mice, to investigate RORalpha1 signalling (and function) in this peripheral tissue. Expression profiling and pathway analysis indicated that RORalpha regulated genes involved in: (i) lipid and carbohydrate metabolism, cardiovascular and metabolic disease; and (ii) the LXR nuclear receptor signaling pathway and, (iii) the Akt and AMPK signaling cascades. This analysis was extensively validated by rigorous qPCR analysis using TaqMan Low Density Arrays, coupled to rigorous statistical analysis (with Empirical Bayes, and Benjamini-Hochberg). Moreover, westerns and metabolic profiling were utilized to validate the genes, proteins and pathways (lipogenic, Akt, AMPK and fatty acid oxidation) involved in the regulation of metabolism by RORalph1. The identified genes and pathways were in concordance with the demonstration of hyperglycemia, glucose intolerance, attenuated insulin stimulated phosphorylation of Akt, and impaired glucose uptake in the transgenic heterozygous Tg-RORalphaâDE animals. In conclusion, we propose that RORalpha1 is involved in regulating the Akt2-AMPK signalling pathways in the context of lipid homeostasis in skeletal muscle. Total RNA was compared from quadriceps femoris of both transgenic and wild type mice. Transgenic mice contained a truncated version of human RORalpha1 (RORalpha1delDE) where the entire E region and part of the hinge/D region have been removed. This transgene is driven by a skeletal muscle specific human skeletal alpha-actin (HSA) promoter.