<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Zhenhua Liu</style></author><author><style face="normal" font="default" size="100%">Brooks, Ryan S</style></author><author><style face="normal" font="default" size="100%">Eric D Ciappio</style></author><author><style face="normal" font="default" size="100%">Susan J Kim</style></author><author><style face="normal" font="default" size="100%">Jimmy W Crott</style></author><author><style face="normal" font="default" size="100%">Grace Bennett</style></author><author><style face="normal" font="default" size="100%">Andrew S Greenberg</style></author><author><style face="normal" font="default" size="100%">Joel B. Mason</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer</style></title><secondary-title><style face="normal" font="default" size="100%">The Journal of Nutritional Biochemistry</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2011</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22209007</style></url></web-urls></urls><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3β was elevated in the colonic mucosa of obese mice (P&lt;.02). Moreover, β-catenin, the key effector of canonical Wnt signaling, was elevated in the colons of obese mice (P&lt;.05), as was the expression of a downstream target gene, c-myc (P&lt;.05). These data demonstrate that diet-induced obesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer.</style></abstract><notes><style face="normal" font="default" size="100%">{PMID:} 22209007</style></notes></record></records></xml>