Interleukin-10 is a protective factor against diet-induced insulin resistance in liver. Export

@article{citeulike:6071867, abstract = {BACKGROUND/AIMS: The anti-inflammatory cytokine, interleukin-10 (IL-10), is known to exert a protective role in hepatic damage caused by viruses, alcohol, autoimmunity and a number of experimental aggressors. Recently, a protective role for IL-10 has also been proposed in diet-induced hepatic dysfunction. However, studies about the mechanisms involved in this process are controversial. The objective of this study was to evaluate the role of endogenous IL-10 in the development of hepatic insulin resistance, associated with diet-induced fatty liver disease. METHODS: Male Swiss mice treated for eight weeks with a high-fat diet became diabetic and developed non-alcoholic fatty liver disease, which is characterized by increased hepatic fat deposition and liver infiltration by F4/80 positive cells. This was accompanied by an increased hepatic expression of TNF-alpha, IL-6, IL-1beta and IL-10, and by an impaired insulin signal transduction through the insulin receptor/IRS1-IRS2/PI3-kinase/Akt/FOXO1 signaling pathway. RESULTS: Upon endogenous IL-10 inhibition for 5 days, using two distinct methods, a neutralizing anti-IL-10 antibody and an antisense oligonucleotide against IL-10, increased hepatic expression of the inflammatory markers TNF-alpha, IL-6, IL-1beta and F4/80 was observed. This was accompanied by a significant negative modulation of insulin signal transduction through insulin receptor/IRS1-IRS2/PI3-kinase/Akt/FOXO1, and by the stimulation of hepatic signaling proteins involved in gluconeogenesis and lipid synthesis. CONCLUSIONS: Thus, in an animal model of diet-induced fatty liver disease, the inhibition of IL-10 promotes the increased expression of inflammatory cytokines, the worsening of insulin signaling and the activation of gluconeogenic and lipidogenic pathways.}, author = {Cintra, Dennys E. and Pauli, Jos\'{e} R. and Ara\'{u}jo, Eliana P. and Moraes, Juliana C. and de Souza, Cl\'{a}udio T. and Milanski, Marciane and Morari, Joseane and Gambero, Alessandra and Saad, M\'{a}rio J. and Velloso, Licio A.}, citeulike-article-id = {6071867}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jhep.2007.12.017}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18267346}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18267346}, doi = {10.1016/j.jhep.2007.12.017}, issn = {0168-8278}, journal = {Journal of hepatology}, keywords = {il-10}, month = {April}, number = {4}, pages = {628--637}, posted-at = {2009-11-05 00:08:55}, priority = {2}, title = {Interleukin-10 is a protective factor against diet-induced insulin resistance in liver.}, url = {http://dx.doi.org/10.1016/j.jhep.2007.12.017}, volume = {48}, year = {2008} }

TY - JOUR ID - citeulike:6071867 L3 - citeulike-article-id:6071867 N2 - BACKGROUND/AIMS: The anti-inflammatory cytokine, interleukin-10 (IL-10), is known to exert a protective role in hepatic damage caused by viruses, alcohol, autoimmunity and a number of experimental aggressors. Recently, a protective role for IL-10 has also been proposed in diet-induced hepatic dysfunction. However, studies about the mechanisms involved in this process are controversial. The objective of this study was to evaluate the role of endogenous IL-10 in the development of hepatic insulin resistance, associated with diet-induced fatty liver disease. METHODS: Male Swiss mice treated for eight weeks with a high-fat diet became diabetic and developed non-alcoholic fatty liver disease, which is characterized by increased hepatic fat deposition and liver infiltration by F4/80 positive cells. This was accompanied by an increased hepatic expression of TNF-alpha, IL-6, IL-1beta and IL-10, and by an impaired insulin signal transduction through the insulin receptor/IRS1-IRS2/PI3-kinase/Akt/FOXO1 signaling pathway. RESULTS: Upon endogenous IL-10 inhibition for 5 days, using two distinct methods, a neutralizing anti-IL-10 antibody and an antisense oligonucleotide against IL-10, increased hepatic expression of the inflammatory markers TNF-alpha, IL-6, IL-1beta and F4/80 was observed. This was accompanied by a significant negative modulation of insulin signal transduction through insulin receptor/IRS1-IRS2/PI3-kinase/Akt/FOXO1, and by the stimulation of hepatic signaling proteins involved in gluconeogenesis and lipid synthesis. CONCLUSIONS: Thus, in an animal model of diet-induced fatty liver disease, the inhibition of IL-10 promotes the increased expression of inflammatory cytokines, the worsening of insulin signaling and the activation of gluconeogenic and lipidogenic pathways. IS - 4 JF - Journal of hepatology SN - 0168-8278 EP - 637 TI - Interleukin-10 is a protective factor against diet-induced insulin resistance in liver. VL - 48 SP - 628 KW - il-10 AU - Cintra, Dennys AU - Pauli, José AU - Araújo, Eliana AU - Moraes, Juliana AU - de Souza, Cláudio AU - Milanski, Marciane AU - Morari, Joseane AU - Gambero, Alessandra AU - Saad, Mário AU - Velloso, Licio PY - 2008/04// UR - http://dx.doi.org/10.1016/j.jhep.2007.12.017 ER -