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SHR Neuro Krebs Kardio Lipid

Prokesch, A; Graef, FA; Madl, T; Kahlhofer, J; Heidenreich, S; Schumann, A; Moyschewitz, E; Pristoynik, P; Blaschitz, A; Knauer, M; Muenzner, M; Bogner-Strauss, JG; Dohr, G; Schulz, TJ; Schupp, M.
Liver p53 is stabilized upon starvation and required for amino acid catabolism and gluconeogenesis.
FASEB J. 2017; 31(2):732-742 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Blaschitz Astrid
Dohr Gottfried
Kahlhofer Jennifer
Madl Tobias
Prokesch Andreas
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Abstract:
The ability to adapt cellular metabolism to nutrient availability is critical for survival. The liver plays a central role in the adaptation to starvation by switching from glucose-consuming processes and lipid synthesis to providing energy substrates like glucose to the organism. Here we report a previously unrecognized role of the tumor suppressor p53 in the physiologic adaptation to food withdrawal. We found that starvation robustly increases p53 protein in mouse liver. This induction was posttranscriptional and mediated by a hepatocyte-autonomous and AMP-activated protein kinase-dependent mechanism. p53 stabilization was required for the adaptive expression of genes involved in amino acid catabolism. Indeed, acute deletion of p53 in livers of adult mice impaired hepatic glycogen storage and induced steatosis. Upon food withdrawal, p53-deleted mice became hypoglycemic and showed defects in the starvation-associated utilization of hepatic amino acids. In summary, we provide novel evidence for a p53-dependent integration of acute changes of cellular energy status and the metabolic adaptation to starvation. Because of its tumor suppressor function, p53 stabilization by starvation could have implications for both metabolic and oncological diseases of the liver.-Prokesch, A., Graef, F. A., Madl, T., Kahlhofer, J., Heidenreich, S., Schumann, A., Moyschewitz, E., Pristoynik, P., Blaschitz, A., Knauer, M., Muenzner, M., Bogner-Strauss, J. G., Dohr, G., Schulz, T. J., Schupp, M. Liver p53 is stabilized upon starvation and required for amino acid catabolism and gluconeogenesis. © The Author(s).

Find related publications in this database (Keywords)
AMPK
hepatic steatosis
liver metabolism
nutrient deprivation
fasting
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