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E-GEOD-474

ABSTRACT: Transcription profiling of human skeletal muscle from obese vs.normal individuals to identify the mRNA of proteins involved in fat oxidation that may be reduced in obese and morbidly obese individuals

OTHER RELATED OMICS DATASETS IN: PRJNA95373PRJNA85153

DISEASE(S): Obesity,Morbidly Obese,Non-obese

PROVIDER: E-GEOD-474 | ExpressionAtlas | 2014-07-03

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-GEOD-474-analysis-methods.tsv	Tabular
	E-GEOD-474-atlasExperimentSummary.Rdata	Rdata
	E-GEOD-474-configuration.xml	Xml
	E-GEOD-474-percentile-ranks.tsv	Tabular
	E-GEOD-474.condensed-sdrf.tsv	Tabular

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Transcription profiling of human skeletal muscle from obese vs.normal individuals to identify the mRNA of proteins involved in fat oxidation that may be reduced in obese and morbidly obese individuals

Project description:It has been found that fat oxidation is reduced in the skeletal muscle of obese humans. This study aims to identify the mRNA of proteins involved in fat oxidation that may be reduced in obese and morbidly obese individuals. Information gathered will help in understanding how obesity contributes to cardiovascular disease via insulin resistance. Samples were obtained from patients undergoing elective abdominal surgery.

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Project description:Alternative mRNA splicing provides transcript diversity and has been proposed to contribute to several human diseases. Here, we demonstrate that expression of genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. To determine the metabolic impact of reduced splicing factor expression, we further evaluated the splicing factor, SFRS10, identified as down-regulated in obese human liver and skeletal muscle and in high fat fed rodents. siRNA-mediated reductions in SFRS10 expression induced lipogenesis and lipid accumulation in cultured hepatocytes. Moreover, SFRS10 heterozygous mice have both increased hepatic lipogenic gene expression and hypertriglyceridemia. We also demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10, with reduced SFRS10 levels favoring the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished the lipogenic effects of decreased SFRS10 expression. Together, our results indicate reduced expression of SFRS10 alters LPIN1 splicing and induces lipogenesis, demonstrating that reduced splicing factor expression observed in human tissues may contribute to metabolic phenotypes associated with human obesity. Skeletal muscle samples were obtained from 10 lean control subjects and 7 obese subjects with either IGT or DM2 undergoing elective cholecystectomy. Data for liver samples presented in the same manuscript are available at GEO GSE15653. In this analysis RNA was isolated for cRNA preparation and hybridized to Affymetrix Human Genome U133 Plus 2.0 microarrays.

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