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Nuclear receptor corepressor RIP140 regulates fat accumulation
Göran Leonardsson1, Jenny H Steel, Mark Christian
1Institute of Reproductive and Developmental Biology, Imperial College London, Du Cane Road, London W12 ONN, United Kingdom.
Summary
The nuclear receptor corepressor RIP140 is essential for maintaining energy balance. Its absence in mice leads to leanness and increased energy expenditure, suggesting RIP140 as a therapeutic target for obesity.
Area of Science:
- Molecular biology
- Metabolism
- Endocrinology
Background:
- Nuclear receptors and coactivators regulate adipose tissue.
- Energy homeostasis involves balancing energy storage and expenditure.
Purpose of the Study:
- Investigate the role of a ligand-dependent transcriptional repressor in energy balance.
- Determine the function of the corepressor protein RIP140 in adipose tissue biology.
Main Methods:
- Mice lacking the RIP140 gene were studied.
- Analysis of metabolic parameters, gene expression, and adipogenesis was performed.
Main Results:
- RIP140-deficient mice were lean, resistant to obesity and hepatic steatosis, and exhibited increased oxygen consumption.
- Lipogenic enzyme expression was reduced, while genes for energy dissipation and mitochondrial uncoupling (e.g., uncoupling protein 1) were increased.
- Adipogenesis was not affected.
Conclusions:
- Transcriptional repression by RIP140 in white adipose tissue is crucial for energy homeostasis.
- Targeting RIP140 recruitment to nuclear receptors offers a potential therapeutic strategy for obesity and related metabolic disorders.