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-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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes / cytology
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Adipocytes / drug effects
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Adipocytes / metabolism
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Adipose Tissue, Brown / cytology*
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Adipose Tissue, Brown / drug effects
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Adipose Tissue, Brown / metabolism*
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Animals
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CCAAT-Enhancer-Binding Protein-beta / genetics
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CCAAT-Enhancer-Binding Protein-beta / metabolism
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Cell Differentiation*
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Cell Line
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Cell Respiration
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Cyclic CMP / analogs & derivatives
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Cyclic CMP / pharmacology
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Cytochromes c / genetics
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Cytochromes c / metabolism
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Gene Expression Profiling
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Gene Expression Regulation
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Ion Channels / genetics
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Ion Channels / metabolism
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Mice
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Mice, Knockout
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Mitochondria / drug effects
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Mitochondria / genetics
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Mitochondria / metabolism*
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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RNA Interference
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RNA, Messenger / metabolism
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Thermogenesis / genetics
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Uncoupling Protein 1
Substances
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CCAAT-Enhancer-Binding Protein-beta
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Ion Channels
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Mitochondrial Proteins
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, mouse
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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Uncoupling Protein 1
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peroxisome-proliferator-activated receptor-gamma coactivator-1
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Cyclic CMP
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dibutyryl cyclic-3',5'-cytidine monophosphate
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Cytochromes c