Lizarbe B.,Instituto Investigaciones Biomedicas Alberto Sols |
Benitez A.,Instituto Investigaciones Biomedicas Alberto Sols |
Benitez A.,Autonomous University of Madrid |
Lago L.,Autonomous University of Madrid |
And 3 more authors.
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Obesity is a pandemic syndrome underlying the most prevalent causes of death and disability in developed countries including atherosclerosis, ischemic episodes and cancer. Obesity results from an imbalance in global energy metabolism, ultimately caused by disturbances in the neuroendocrine control of appetite in the hypothalamus and leading to an uncompensated feeding/fasting balance . On these grounds, the non invasive detection of hypothalamic activation by food under healthy or diseased conditions entails considerable interest for the diagnosis and treatment of obesity and other food intake disorders as anorexia or bulimia. © 2011 Springer-Verlag Berlin Heidelberg. Source
Sanz-Garcia C.,Instituto Investigaciones Biomedicas Alberto Sols |
Ferrer-Mayorga G.,Instituto Investigaciones Biomedicas Alberto Sols |
Gonzalez-Rodriguez A.,Instituto Investigaciones Biomedicas Alberto Sols |
Gonzalez-Rodriguez A.,Research Center Biomedica En Red Of Diabetes fermedades Metabolicas Asociadas |
And 7 more authors.
Journal of Biological Chemistry
Cot/tpl2 (MAP3K8) activates MKK1/2-Erk1/2 following stimulation of the Toll-like/IL-1 receptor superfamily. Here, we investigated the role of Cot/tpl2 in sterile inflammation and drug-induced liver toxicity. Cot/tpl2 KO mice exhibited reduced hepatic injury after acetaminophen challenge, as evidenced by decreased serum levels of both alanine and aspartate aminotransferases, decreased hepatic necrosis, and increased survival relative to Wt mice. Serum levels of both alanine and aspartate aminotransferases were also lower after intraperitoneal injection of acetaminophen in mice expressing an inactive form of Cot/tpl2 compared with Wt mice, suggesting that Cot/tpl2 activity contributes to acetaminophen-induced liver injury. Furthermore, Cot/tpl2 deficiency reduced neutrophil and macrophage infiltration in the liver of mice treated with acetaminophen, as well as their hepatic and systemic levels of IL-1α. Intraperitoneal injection of damage-associated molecular patterns from necrotic hepatocytes also impaired the recruitment of leukocytes and decreased the levels of several cytokines in the peritoneal cavity in Cot/tpl2 KO mice compared with Wt counterparts. Moreover, similar activation profiles of intracellular pathways were observed in Wt macrophages stimulated with Wt or Cot/tpl2 KO damage-associated molecular patterns. However, upon stimulation with damage-associated molecular patterns, the activation of Erk1/2 and JNK was deficient in Cot/tpl2 KO macrophages compared with their Wt counterparts; an effect accompanied by weaker release of several cytokines, including IL-1α, an important component in the development of sterile inflammation. Taken together, these findings indicate that Cot/tpl2 contributes to acetaminophen-induced liver injury, providing some insight into the underlying molecular mechanisms. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Source