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Twist-1 Is a PPARδ-Inducible, Negative-Feedback Regulator of PGC-1α in Brown Fat Metabolism
Open accessAbstract
Summary Brown fat is specialized in energy expenditure, a process that is principally controlled by the transcriptional co-activator PGC-1α. Here we describe a molecular network important for PGC-1α function and brown fat metabolism. We find that twist-1 is selectively expressed in adipose tissue, interacts with PGC-1α, and is recruited to the promoters of PGC-1α’s target genes to suppress mitochondrial metabolism and uncoupling. In vivo, transgenic mice expressing twist-1 in the adipose tissue are prone to high-fat diet induced obesity, whereas twist-1 heterozygous knockout mice are obesity-resistant. These phenotypes are attributed to their altered mitochondrial metabolism in the brown fat. Interestingly, the nuclear receptor PPARδ not only mediates the actions of PGC-1α, but also regulates twist-1 expression, suggesting a negative feedback regulatory mechanism. These findings reveal an unexpected physiological role for twist-1 in the maintenance of energy homeostasis and have important implications for understanding metabolic control and metabolic diseases.
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Metadata
- Authors
- Pan, D., Fujimoto, M., Lopes, A., & Wang, Y.-X.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 137
- Issue
- 1
- Pages
- 73-86
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2141791765
- Cited by
- 218
- References
- 19
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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