Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep34542
Keywords
-
Categories
Funding
- Spanish Ministry of Education
- Spanish Association Against Cancer (aecc)
- CNIO
- Spanish Ministry of Economy
- European Regional Development Fund (SAF project)
- European Research Council (ERC Advanced Grant)
- Regional Government of Madrid
- European Social Fund (ReCaRe project)
- Botin Foundation
- Banco Santander (Santander Universities Global Division)
- Ramon Areces Foundation
- AXA Foundation
Ask authors/readers for more resources
Fasting is a physiological stress that elicits well-known metabolic adaptations, however, little is known about the role of stress-responsive tumor suppressors in fasting. Here, we have examined the expression of several tumor suppressors upon fasting in mice. Interestingly, p21 mRNA is uniquely induced in all the tissues tested, particularly in liver and muscle (>10 fold), and this upregulation is independent of p53. Remarkably, in contrast to wild-type mice, p21-null mice become severely morbid after prolonged fasting. The defective adaptation to fasting of p21-null mice is associated to elevated energy expenditure, accelerated depletion of fat stores, and premature activation of protein catabolism in the muscle. Analysis of the liver transcriptome and cell-based assays revealed that the absence of p21 partially impairs the transcriptional program of PPAR alpha, a key regulator of fasting metabolism. Finally, treatment of p21-null mice with a PPAR alpha agonist substantially protects them from their accelerated loss of fat upon fasting. We conclude that p21 plays a relevant role in fasting adaptation through the positive regulation of PPAR alpha.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available