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Series GSE8157 Query DataSets for GSE8157
Status Public on Nov 10, 2008
Title Gene expression profiling in skeletal muscle of PCOS after pioglitazone therapy
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZD) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZD in PCOS is in part mediated by changes in the transcriptional profile of muscle favoring insulin sensitivity.
Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp. Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy control women. Treatment with pioglitazone improved insulin-stimulated total, oxidative and non-oxidative glucose metabolism, and reduced fasting serum insulin (all p < 0.05). Global pathway analysis using Gene Map Annotator and Pathway Profiler (GenMAPP 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1) revealed a significant upregulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome, translation factors, and proteasome complexes in PCOS patients after pioglitazone therapy. Quantitative real-time PCR suggested that upregulation of OXPHOS genes was mediated by an increase in PGC-1α expression (p < 0.05). Expression of genes involved in ribosomal proteins and OXPHOS was down-regulated in PCOS patients before treatment compared to matched healthy women using GenMAPP 2.1 and GSEA 2.1.
These data indicate that pioglitazone therapy restores insulin sensitivity in part by a coordinated upregulation of genes involved in mitochondrial oxidative metabolism and protein biosynthesis in skeletal muscle of PCOS. These transcriptional effects of pioglitazone therapy may contribute to prevent the onset of type 2 diabetes in these women.
Keywords: PCOS, microarray, global pathway analysis, insulin resistance, pioglitazone, protein metabolism, mitochondrial oxidative metabolism
Overall design Ten obese women of reproductive age with PCOS participated in the study to test the effect of pioglitazone therapy (data set 1). To test if pioglitazone ameliorate existing defects in PCOS patients, the expression profile of the 10 PCOS patients before treatment were compared to the same cohort of 13 control subjects (data set 2).
Contributor(s) Skov V, Glintborg D, Knudsen S, Tan Q, Jensen T, Kruse TA, Beck-Nielsen H, Højlund K
Citation(s) 18560589
Submission date Jun 18, 2007
Last update date Mar 25, 2019
Contact name Vibe Skov
Phone +4526178735
Organization name Roskilde Hospital
Department Hematology
Street address Koegevej 7-13
City Roskilde
ZIP/Postal code 4000
Country Denmark
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (43)
GSM201542 Muscle PCOS pioglitazone 101
GSM201543 Muscle PCOS pioglitazone 121
GSM201544 Muscle PCOS pioglitazone 161
BioProject PRJNA101043

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Supplementary file Size Download File type/resource
GSE8157_RAW.tar 349.3 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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