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Supplemental carnitine affects the microRNA expression profile in skeletal muscle of obese Zucker rats

ABSTRACT: Background In the past, numerous studies revealed that supplementation with carnitine has multiple effects on performance characteristics and gene expression in livestock and model animals. The molecular mechanisms underlying these observations are still largely unknown. Increasing evidence suggests that microRNAs (miRNAs), a class of small non-coding RNA molecules, play an important role in post-transcriptional regulation of gene expression and thereby influencing several physiological and pathological processes. Based on these findings, the aim of the present study was to investigate the influence of carnitine supplementation on the miRNA expression profile in skeletal muscle of obese Zucker rats using miRNA microarray analysis. Results miRNA expression profiling in skeletal muscle revealed a subset of 152 miRNAs out of the total number of miRNAs analysed (259) were identified to be differentially regulated (adjusted P-value ˂ 0.05) by carnitine supplementation. Compared to the obese control group, 111 miRNAs were up-regulated and 41 down-regulated by carnitine supplementation (adjusted P-value ˂ 0.05). 14 of these miRNAs showed a log2 ratio ≥ 0.5 and 7 miRNAs showed a log2 ratio ≤ -0.5 (adjusted P-value ˂ 0.05). Conclusion The present study shows for the first time that supplementation of carnitine affects a large set of miRNAs in skeletal muscle of obese Zucker rats suggesting a novel mechanism through which carnitine exerts its multiple effects on gene expression, which were observed during the past.

ORGANISM(S): synthetic construct Rattus norvegicus

PROVIDER: GSE58537 | GEO | 2014/06/17

SECONDARY ACCESSION(S): PRJNA252843

REPOSITORIES: GEO

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Project description:Purpose: To identify, using RNA-sequencing, differentially expressed genes in the white adipose tissue in obesity and in response to lipid intervention in both normal weight and obese individuals. Methods: White adipose tissue mRNA profiles of normal weight and obses humans at baseline (0-weeks) and 12-weeks after fish oil (3d/day of which 1.1g EPA and 0.8g DHA) or corn oil (3g/day) supplementation were generated by deep sequencing using RNA sequencing. The sequence reads that passed quality filters were aligned to the human genome using TopHat and analyzed at the gene level using DESeq2. qRT–PCR validation was performed using Taqman probe assays Results: Using an optimized data analysis workflow, we mapped reads to the human genome (hg38.0) and identified 789 genes differentially expressed between normal weight and obese individuals at baseline (week-0) (adjusted p value <0.05 and fold change >2). 623 of these were upregulated and 175 were downregulated. Geneset enrichment analysis identified several enriched pathways, including regulation of immune and inflammatory response, tissue growth and glucose metabolism in obese indvidiuals in comparison to normal weight. We identified 26 genes differentially expressed in normal weight individuals in response to fish oil intervention (week-12) (adjusted p value <0.05 and fold change >1). 14 of these were upregulated and 12 were downregulated. We identified 8 genes differentially expressed in obese individuals in response to fish oil intervention (week-12) (adjusted p value <0.05 and fold change >1). 3 of these were upregulated and 5 were downregulated. Geneset enrichment analysis identified several enriched pathways, including regulation of immune and inflammatory response in both normal weight and obese individuals in response to fish oil intervention with greater effects in normal weight individuals. Conclusions: Our study provides novel insights into the association of obesity and changes to the human white adipose tissue transcriptome, in addition to the effects of fish oil (EPA and DHA) on the transcriptome of normal weight and obese individuals and differences in response between these BMI subgroups. Our study further identifies putative gene targets and molecular pathways that help to understand how obesity results in adipose tissue dysfunction and how EPA and DHA may modulate the long term expression of gene networks and disease pathways related to onset of obesity associated inflammation.

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Supplemental carnitine affects the microRNA expression profile in skeletal muscle of obese Zucker rats

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