Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of wild type and PGC-1 alpha knockout mouse mature brown adipocytes treated with or without dibutyryl cAMP to investigate the specific role of PGC-1 coactivators in brown fat cells

ABSTRACT: To investigate the specific role of PGC-1 coactivators in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1alpha. We could then efficiently knockdown PGC-1beta expression by shRNA expression. Loss of PGC-1alpha did not alter brown fat differentiation but severly reduced the induction of thermogenic genes. In order to assess the specific requirement for PGC-1± in the global transcriptional response to cAMP, we used Affymetrix arrays to compare the sets of genes induced in response to a 4 hr dbcAMP treatment in differentiated wt and KO cells. This analysis revealed that 88 genes were induced more than 3-fold in the wt cells; of these, 54 (61% of total) were similarly increased in both wt and KO. However, 28 genes (32% of total) were decreased by at least 50% in the KO cells compared to wt cells. These data were confirmed by quantitative PCR for a subset of genes. These data indicate that PGC-1± is required for proper expression of approximately one third of the genes induced in response to cAMP in brown fat cells, but this set of sensitive genes is enriched in those involved in adaptative thermogenesis. Experiment Overall Design: WT and PGC-1alpha KO brown preadipocytes were differentiated into mature brown adipocytes for seven days. Cells were then treated with dibutyryl cAMP for four hours. Two replicates were made for each condition: WT non treated, WT treated with cAMP, KO non treated, KO treated with cAMP. Transcription profiling of wild type and PGC-1 alpha knockout mouse mature brown adipocytes treated with dibutyryl cAMP to investigate the specific role of PGC-1 coactivators in brown fat cells

ORGANISM(S): Mus musculus

SUBMITTER: Marc Uldry

PROVIDER: E-GEOD-5041 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation.

Uldry Marc M Yang Wenli W St-Pierre Julie J Lin Jiandie J Seale Patrick P Spiegelman Bruce M BM

Cell metabolism 20060501 5

Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1alpha. We could then efficiently knockdown PGC-1beta expression by shRNA expression. Loss of PGC-1alpha did not alter brown fat differentiation but severely reduced the induction of thermoge ...[more]

PMID: 16679291

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Project description:Title: Total Skeletal Muscle PGC-1 Deficiency Uncouples Mitochondrial Derangements from Fiber Type Determination and Insulin Sensitivity Abstract: Evidence is emerging that the PGC-1 coactivators serve a critical role in skeletal muscle metabolism, function, and disease. Mice with total PGC-1 deficiency in skeletal muscle (PGC-1α-/- βf/f/MLC-Cre mice) were generated and characterized. PGC-1α-/-βf/f/MLC-Cre mice exhibit a dramatic reduction in exercise performance compared to single PGC-1α- or PGC-1β-deficient mice and wild-type controls. The exercise phenotype of the PGC-1α-/-βf/f/MLC-Cre mice was associated with a marked diminution in muscle oxidative capacity and mitochondrial structural derangements consistent with fusion/fission and biogenic defects together with rapid depletion of muscle glycogen stores during exercise. Surprisingly, the skeletal muscle fiber type profile of the PGC-1α-/-βf/f/MLCCre mice was not significantly different than the wild-type mice. Moreover, insulin sensitivity and glucose tolerance were also not altered in the PGC-1α-/-βf/f/MLC-Cre mice. Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity. RNA from PGC-1alpha-/- beta f/f/Mlc1fcre was obtained and gene expression pattern compared with PGC-1alpha -/-, PGC-1beta f/f, and PGC-1beta f/f/Mlc1fCre controls. Results file descriptions: 1. GSE23365_skfloxAKO_PPexcl_genesup_GEO-8-16-2010: This table contains genes that were upregulated ≥2.0 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names. 2. GSE23365_skfloxAKO_PPexcl_genesdown_GEO-8-16-2010 This table contains genes that were downregulated ≤0.7 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names.