2026-06-14T03:38:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66912024-09-27T07:59:07Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Porteiro, Begona
author
Fondevila, Marcos F.
author
Buque, Xabier
author
Gonzalez-Rellan, Maria J.
author
Fernandez, Uxia
author
Mora, Alfonso
author
Beiroa, Daniel
author
Senra, Ana
author
Gallego, Rosalia
author
Ferno, Johan
author
Lopez, Miguel
author
Sabio, Guadalupe
author
Dieguez, Carlos
author
Aspichueta, Patricia
author
Nogueiras, Ruben
funder
Ministerio de Economía y Competitividad (España)
funder
Xunta de Galicia (España)
funder
Heise Vest RHF
funder
Comunidad de Madrid (España)
funder
Basque Government (España)
funder
Fundación AstraZeneca
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea
funder
Centro de Investigación Biomedica en Red - CIBER
2018-11-22T08:10:54Z
2018-11-22T08:10:54Z
2018
Mol Metab. 2018; 8:132-143
10.1016/j.molmet.2017.12.005
2212-8778
Molecular Metabolism
29290620
http://hdl.handle.net/20.500.12105/6691
Objective: Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Methods: We used long-term pharmacological activation of p53 by i.p. or oral administration of low-dose doxorubicin in different animal models of NAFLD (high fat diet containing 45\% and 60\% kcal fat) and NASH (methionine- and choline-deficient diet and choline deficiency combined with high fat diet). We also administered doxorubicin in mice lacking p53 in the liver and in two human hepatic cells lines (HepG2 and THLE2). Results: The attenuation of liver damage was accompanied by the stimulation of fatty acid oxidation and decrease of lipogenesis, inflammation, and ER stress. The effects of doxorubicin were abrogated in mice with liver-specific ablation of p53. Finally, the effects of doxorubicin on lipid metabolism found in animal models were also present in two human hepatic cells lines, in which the drug stimulated fatty acid oxidation and inhibited de novo lipogenesis at doses that did not cause changes in apoptosis or cell viability. Conclusion: These data provide new evidence for targeting p53 as a strategy to treat liver disease. (C) 2017 The Authors. Published by Elsevier GmbH.
eng
Obesity
Lipid metabolism
Inflammation
Pharmacological stimulation of p53 with low-dose doxorubicin ameliorates diet-induced nonalcoholic steatosis and steatohepatitis
journal article
URL
https://repisalud.isciii.es/bitstreams/952b9746-4072-46de-bc8e-ab142cb2973c/download
File
MD5
02fc73184090d8a30f9aef690b5da1ca
5322392
application/pdf
PharmacologicalStimulationfoP53_2018.pdf
URL
https://repisalud.isciii.es/bitstreams/f9db9c44-0b6f-4d91-8e96-7bc55e320be5/download
File
MD5
617e2a3596df04003ec60bf85452cc42
446813
application/pdf
PharmacologicalStimulationfoP53_2018-mmc1.pdf
URL
https://repisalud.isciii.es/bitstreams/6d9b0c92-e569-478f-8f1d-2a12213d76e1/download
File
MD5
b1aee8f034c0faeea736283b702ce082
287050
image/jpeg
PharmacologicalStimulationfoP53_2018-figs1_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/81ec7ecb-8507-46d1-8231-35569a810986/download
File
MD5
da996e6d1d3c583ee4a29f2df7d0da9e
732524
image/jpeg
PharmacologicalStimulationfoP53_2018-figs2_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/85e18a3e-ffc3-4803-ae7a-7a5e04c2a7be/download
File
MD5
4d130e21b49a8a21bcbcdab25a3b3e19
563931
image/jpeg
PharmacologicalStimulationfoP53_2018-figs3_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/c783142f-f87b-4f82-b6a8-549e65a759a8/download
File
MD5
d72e55d719f660899fbfa89b1e8d2308
338193
image/jpeg
PharmacologicalStimulationfoP53_2018-figs4_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/ce3e6337-2e69-4413-b8b0-83b6f91fd65f/download
File
MD5
4359f5421c67c174eb5d340ebcc362cd
627621
image/jpeg
PharmacologicalStimulationfoP53_2018-figs5_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/dc2c7052-e01d-470d-b8fc-b685c099a3a4/download
File
MD5
a8707f9a11d0e9bdf2a7513a2f23350c
267157
image/jpeg
PharmacologicalStimulationfoP53_2018-figs6_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/e894afa2-b41e-4062-a686-9c32ad7dea19/download
File
MD5
2cfa598b3e8e6548f75a2fa81db50fec
817036
image/jpeg
PharmacologicalStimulationfoP53_2018-figs7_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/36d6ba15-a0d3-4793-96fa-2244dd893e2b/download
File
MD5
105c79ececae275a46808ba2e366a1dc
780360
image/jpeg
PharmacologicalStimulationfoP53_2018-figs8_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/c0303227-2c94-461a-9ace-b435eeadd481/download
File
MD5
0bf78520071d2989741c6b28576418d2
701360
image/jpeg
PharmacologicalStimulationfoP53_2018-figs9_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/674a2d38-2ea5-42e5-8a75-057eda9bc1f2/download
File
MD5
64b8121864542428edf0f3a8cf1821f1
712054
image/jpeg
PharmacologicalStimulationfoP53_2018-figs10_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/b311b9c6-e805-4c7b-a450-01bb93819f26/download
File
MD5
d1969256685ecf09c315b818caf68b0b
672639
image/jpeg
PharmacologicalStimulationfoP53_2018-figs11_lrg.jpg
URL
https://repisalud.isciii.es/bitstreams/3c760347-98b0-4c26-8797-176d8305270e/download
File
MD5
e6b683ac20b30bccc1dc5d131b1b4f1d
49379
text/plain
PharmacologicalStimulationfoP53_2018.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/3f4fcd4e-d235-4296-8001-d77bbb139759/download
File
MD5
2813f52fdfbf8d68c6a8d8daa9af8f51
18259
text/plain
PharmacologicalStimulationfoP53_2018-mmc1.pdf.txt