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The Transcriptional Coregulators TIF2 and SRC-1 Regulate Energy Homeostasis by Modulating Mitochondrial Respiration in Skeletal Muscles
- Source :
- Cell Metabolism. 12:496-508
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Summary 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.
- Subjects :
- medicine.medical_specialty
Transcription, Genetic
Physiology
Cell Respiration
Adipose tissue
Mitochondrion
Biology
Ion Channels
Article
Energy homeostasis
Mitochondrial Proteins
Nuclear Receptor Coactivator 2
Nuclear Receptor Coactivator 1
Myofibrils
Internal medicine
medicine
Uncoupling Protein 3
Uncoupling protein
Myocyte
Obesity
Muscle, Skeletal
Molecular Biology
UCP3
Skeletal muscle
Cell Biology
Mitochondria
medicine.anatomical_structure
Endocrinology
Diabetes Mellitus, Type 2
Gene Expression Regulation
Energy Metabolism
Myofibril
Oxidation-Reduction
Gene Deletion
Subjects
Details
- ISSN :
- 15504131
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cell Metabolism
- Accession number :
- edsair.doi.dedup.....3278a15dd49f64f8a03da62766750646