Abstract：
:The two p160 transcriptional coregulator family members SRC-1 and TIF2 have important metabolic functions in white and brown adipose tissues as well as in the liver. To analyze TIF2 cell-autonomous functions in skeletal muscles, we generated TIF2((i)skm)⁻(/)⁻ mice in which TIF2 was selectively ablated in skeletal muscle myofibers at adulthood. We found that increased mitochondrial uncoupling in skeletal muscle myocytes protected these mice from decreased muscle oxidative capacities induced by sedentariness, delayed the development of type 2 diabetes, and attenuated high-caloric-diet-induced obesity. Moreover, our results demonstrate that SRC-1 and TIF2 can modulate the expression of the uncoupling protein 3 (UCP3) in an antagonistic manner and that enhanced SRC-1 levels in TIF2-deficient myofibers are critically involved in the metabolic changes of TIF2((i)skm)⁻(/)⁻ mice. Thus, modulation of the expression and/or activity of these coregulators represents an attractive way to prevent or treat metabolic disorders.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Duteil D,Chambon C,Ali F,Malivindi R,Zoll J,Kato S,Geny B,Chambon P,Metzger Ddoi
10.1016/j.cmet.2010.09.016subject
Has Abstractpub_date
2010-11-03 00:00:00pages
496-508issue
5eissn
1550-4131issn
1932-7420pii
S1550-4131(10)00352-9journal_volume
12pub_type
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