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Effect of L-carnitine administration on lipid and metabolite content in sheep infraspinatus muscle after tendon release

ABSTRACT: Metabolites and lipid species were measured using ultrahigh performance lipid chromatography – tandem mass spectrometry in biopsies of infraspinatus muscle after 2 weeks of tendon release in the operated and contralateral muscle. A group of animals received oral treatment with L-carnitine.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS1490 | MetaboLights | 2020-07-20

REPOSITORIES: MetaboLights

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			Action	DRS
	jh_20180306_p1719_4099_10_HILIC_pH9_6120_KL_P.raw.zip	Raw
	jh_20180306_p1719_4099_11_HILIC_pH9_6121_OPS_P.raw.zip	Raw
	jh_20180306_p1719_4099_12_HILIC_pH9_6121_KL_P.raw.zip	Raw
	jh_20180306_p1719_4099_1_HILIC_pH9_2940_OPS_P.raw.zip	Raw
	jh_20180306_p1719_4099_2_HILIC_pH9_2940_KL_P.raw.zip	Raw

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Project description:Aims/hypothesis: While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression M-bM-^@M-^S in comparison with effects of PLIN2 M-bM-^@M-^S on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. Methods: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. Results: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPARM-NM-1 and PGC1M-NM-1 involved in FA catabolism and mitochondrial oxidation. Rats received a high fat diet for 3 weeks; 2 weeks after start of the diet intervention Plin5 (OXPAT) or Plin2 (ADRP) were overexpressed in either the right or left tibialis anterior muscle. One week later pooled tibialis anterior muscle samples were analysed on microarrays.

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.

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Effect of L-carnitine administration on lipid and metabolite content in sheep infraspinatus muscle after tendon release

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