Critical roles of the p160 transcriptional coactivators p/CIP and SRC-1 in energy balance
| Autor: | Tony Hunter, Anna Krones, Chao Qi, Michael G. Rosenfeld, Zhi-Yong Wang, Pamela J. Woodring, Ronald M. Evans, Xiaoyan Zhu, Janardan K. Reddy |
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| Rok vydání: | 2004 |
| Předmět: |
Leptin
medicine.medical_specialty Chromatin Immunoprecipitation Physiology HUMDISEASE Enzyme-Linked Immunosorbent Assay Biology Motor Activity Energy homeostasis Nuclear Receptor Coactivator 3 Basal (phylogenetics) Eating Mice Nuclear Receptor Coactivator 1 Adipose Tissue Brown Internal medicine medicine Animals Homeostasis Gene Molecular Biology Triglycerides DNA Primers Histone Acetyltransferases Mice Knockout Adipogenesis Thermogenesis DNA Cell Biology Blotting Northern In vitro Endocrinology Nuclear receptor Gene Expression Regulation Trans-Activators Basal Metabolism Energy Metabolism Proto-oncogene tyrosine-protein kinase Src Transcription Factors |
| Zdroj: | Cell metabolism. 3(2) |
| ISSN: | 1550-4131 |
| Popis: | Summary Several transcriptional coactivators have been implicated in modulating the transcriptional activities of nuclear hormone receptors in vitro. Potential roles of these cofactors in important physiological processes such as energy homeostasis remain unknown. We report here that a developmental arrest in interscapular brown fat and defective adaptive thermogenesis occur in mice lacking both the p160 family transcriptional coactivators SRC-1 and p/CIP due to a failure in induction of selective PPARγ target genes involved in adipogenesis and mitochondrial uncoupling. In the absence of p/CIP and SRC-1, mice eat more food on both regular chow and a high-fat diet because of decreased blood leptin levels. However, the p/CIP −/− /SRC-1 −/− mice are lean and resistant to high-fat-diet-induced obesity. They exhibit increased basal metabolic rates and heightened levels of physical activity. Therefore, p/CIP and SRC-1 play critical roles in energy balance by controlling both energy intake and energy expenditure. |
| Databáze: | OpenAIRE |
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