SRC-1 and TIF2 control energy balance between white and brown adipose tissues.
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.
Picard
Frédéric
F
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France.
Géhin
Martine
M
Annicotte
Jean- Sébastien
J
Rocchi
Stéphane
S
Champy
Marie-France
MF
O'Malley
Bert W
BW
Chambon
Pierre
P
Auwerx
Johan
J
D017667:Adipocytes / Q000378:metabolism / Q000648:ultrastructure; D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000235:genetics*; D051548:Histone Acetyltransferases; D050356:Lipid Metabolism; D008066:Lipolysis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D022722:Thermogenesis / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1