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p21(Cip1) plays a critical role in the physiological adaptation to fasting through activation of PPARα.

Lopez-Guadamillas, E; Fernandez-Marcos, PJ; Pantoja, C; Muñoz-Martin, M; Martínez, D; Gómez-López, G; Campos-Olivas, R; ... Serrano, M; + view all (2016) p21(Cip1) plays a critical role in the physiological adaptation to fasting through activation of PPARα. Sci Rep , 6 , Article 34542. 10.1038/srep34542. Green open access

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Abstract

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 PPARα, a key regulator of fasting metabolism. Finally, treatment of p21-null mice with a PPARα 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 PPARα.

Type: Article
Title: p21(Cip1) plays a critical role in the physiological adaptation to fasting through activation of PPARα.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/srep34542
Publisher version: http://dx.doi.org/10.1038/srep34542
Language: English
Additional information: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Cell biology, Molecular biology
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/1521335
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