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

      Cell Metabolism

      Adipocytes, cytology, drug effects, metabolism, Adipose Tissue, Brown, Animals, CCAAT-Enhancer-Binding Protein-beta, genetics, Cell Differentiation, Cell Line, Cell Respiration, Cyclic CMP, analogs & derivatives, pharmacology, Cytochromes c, Gene Expression Profiling, Gene Expression Regulation, Ion Channels, Mice, Mice, Knockout, Mitochondria, Mitochondrial Proteins, Oligonucleotide Array Sequence Analysis, RNA Interference, RNA, Messenger, Thermogenesis, Trans-Activators, Transcription Factors

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          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 thermogenic genes. Cells deficient in either PGC-1alpha or PGC-1beta 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-1alpha and PGC-1beta were deficient. These data show that PGC-1alpha 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.

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