Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of differentiated brown adipocytes from wild type, PGC-1 alpha knockout, or PGC-1 alpha knockout and PGC-1 beta knockdown mice to investigate the roles of PGC-1 coactivators in brown fat differentiation.

ABSTRACT: 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-1±. We could then efficiently knockdown PGC-1Î² expression by shRNA expression. Loss of PGC-1± did not alter brown fat differentiation but severely reduced the induction of thermogenic genes. Cells deficient in either PGC-1Î± or PGC-1Î² coactivators showed a small decrease in the differentiation-dependant program of mitochondrial biogenesis and respiration; however, this increase in mitochondrial number and function was totally abolished during brown fat differentiation when both PGC-1± and PGC-1 were deficient. These data show that PGC-1± is essential for brown fat thermogenesis but not brown fat differentiation, and the PGC-1 coactivators play an absolutely essential but complementary function in differentiation-induced mitochondrial biogenesis. Affymetrix microarray analysis of total RNA from wt, PGC-1± KO and PGC-1± KO; cells expressing an RNAi specific for PGC-1 knockdown was performed. Of the 461; mitochondrial genes analyzed, 181 were found to be at least 20% different between wt; and defective PGC-1± and Î² adipocytes (p < 0.05). More than 85% of these genes were downregulated in cells deficient for PGC-1alpha and PGC-1beta. Experiment Overall Design: Brown preadipocytes that were either WT, KO for PGC-1alpha, or KO for PGC-1alpha and deficient for PGC-1beta (knockdown through siRNA expression) were differentiated for seven days. RNA was made from biological replicates of the three different types of brown adipocytes (WT, KO expressing a control siRNA, KO expressing a siRNA specific for PGC-1beta knockdown).

ORGANISM(S): Mus musculus

SUBMITTER: Marc Uldry

PROVIDER: E-GEOD-5042 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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.

Dataset Information

Transcription profiling of differentiated brown adipocytes from wild type, PGC-1 alpha knockout, or PGC-1 alpha knockout and PGC-1 beta knockdown mice to investigate the roles of PGC-1 coactivators in brown fat differentiation.

Publications

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

Similar Datasets

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