Abstract
We have explored the effects of two members of the p160 coregulator family on energy homeostasis. TIF2-/- mice are protected against obesity and display enhanced adaptive thermogenesis, whereas SRC-1-/- mice are prone to obesity due to reduced energy expenditure. In white adipose tissue, lack of TIF2 decreases PPARgamma activity and reduces fat accumulation, whereas in brown adipose tissue it facilitates the interaction between SRC-1 and PGC-1alpha, which induces PGC-1alpha's thermogenic activity. Interestingly, a high-fat diet increases the TIF2/SRC-1 expression ratio, which may contribute to weight gain. These results reveal that the relative level of TIF2/SRC-1 can modulate energy metabolism.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adipocytes / metabolism
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Adipocytes / ultrastructure
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Adipose Tissue, Brown / metabolism*
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Adipose Tissue, Brown / ultrastructure
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Animals
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Body Weight
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Cells, Cultured
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Energy Metabolism / genetics*
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Histone Acetyltransferases
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Lipid Metabolism
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Lipolysis / genetics
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Male
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Mice
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Mice, Knockout
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Microscopy, Electron
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Molecular Sequence Data
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Nuclear Receptor Coactivator 1
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Nuclear Receptor Coactivator 2
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Obesity / genetics*
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Obesity / metabolism*
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Oxygen Consumption / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Thermogenesis / genetics
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Transcription Factors / deficiency*
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Ncoa2 protein, mouse
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Nuclear Receptor Coactivator 2
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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peroxisome-proliferator-activated receptor-gamma coactivator-1
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Histone Acetyltransferases
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Ncoa1 protein, mouse
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Nuclear Receptor Coactivator 1