On Thursday 15 March 2018, at the XIV Congress of the Spanish Society for the Study of the Obesity (SEEDO) Guadalupe Sabio (Centro Nacional de Investigaciones Cardiovasculares Carlos III) and Amaia Rodríguez Murueta-Goyena (Clínica Universidad de Navarra) will debate about which is the main organ orchestrating the diseases caused by obesity.
Begoña Porteiro, Marcos F. Fondevila, Xabier Buque, Maria J. Gonzalez-Rellan, Uxia Fernandez, Alfonso Mora, Daniel Beiroa, Ana, Senra, Rosalia Gallego, Johan Fernø, Miguel López, Guadalupe Sabio, Carlos Dieguez, Patricia Aspichueta & Rubén Nogueiras.
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).
Hematoxylin&eosin and oil red O staining of liver sections.
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).
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.
These data provide new evidence for targeting p53 as a strategy to treat liver disease
Our lab mate María Crespo has been awarded the second prize in the Archimedes Competition. She will receive a prize of € 2,000.
María Crespo
The competition, organized by the Spanish Ministry of Education, favours the incorporation of young students into the research field by awarding them for their original Master projects of scientific or technological research. On this occasion, more than 350 students throughout Spain participated, of which only 25 went to the final.
Under the supervision of Guadalupe Sabio and Magdalena Leiva, Crespo has studied the circadian rhythm of neutrophil infiltration in the liver and the possible role that these cells play in the regulation of hepatic activity. Through the use of neutropenic mice, she has analyzed the contribution of neutrophils in the progress of non-alcoholic fatty liver disease (NAFLD).
María Crespo among other finalists of the Archimedes Competition.
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