<?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%">James W Perfield</style></author><author><style face="normal" font="default" size="100%">Yunkyoung Lee</style></author><author><style face="normal" font="default" size="100%">Gerald I Shulman</style></author><author><style face="normal" font="default" size="100%">Varman T Samuel</style></author><author><style face="normal" font="default" size="100%">Michael J Jurczak</style></author><author><style face="normal" font="default" size="100%">Eugene Chang</style></author><author><style face="normal" font="default" size="100%">Chen Xie</style></author><author><style face="normal" font="default" size="100%">Phillip N Tsichlis</style></author><author><style face="normal" font="default" size="100%">Martin S Obin</style></author><author><style face="normal" font="default" size="100%">Andrew S Greenberg</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Tumor Progression Locus 2 (TPL2) Regulates Obesity-Associated Inflammation and Insulin Resistance</style></title><secondary-title><style face="normal" font="default" size="100%">Diabetes</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/21346175</style></url></web-urls></urls><number><style face="normal" font="default" size="100%">4</style></number><volume><style face="normal" font="default" size="100%">60</style></volume><pages><style face="normal" font="default" size="100%">1168–1176</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">OBJECTIVE Obesity-associated low-grade systemic inflammation resulting from increased adipose mass is strongly related to the development of insulin resistance and type 2 diabetes as well as other metabolic complications. Recent studies have demonstrated that the obese metabolic state can be improved by ablating certain inflammatory signaling pathways. Tumor progression locus 2 (TPL2), a kinase that integrates signals from Toll receptors, cytokine receptors, and inhibitor of κ-B kinase-β is an important regulator of inflammatory pathways. We used TPL2 knockout (KO) mice to investigate the role of TPL2 in mediating obesity-associated inflammation and insulin resistance. 

RESEARCH DESIGN AND METHODS Male {TPL2KO} and wild-type {(WT)} littermates were fed a low-fat diet or a high-fat diet to investigate the effect of {TPL2} deletion on obesity, inflammation, and insulin sensitivity. {RESULTS} We demonstrate that {TPL2} deletion does not alter body weight gain or adipose depot weight. However, hyperinsulinemic euglycemic clamp studies revealed improved insulin sensitivity with enhanced glucose uptake in skeletal muscle and increased suppression of hepatic glucose output in obese {TPL2KO} mice compared with obese {WT} mice. Consistent with an improved metabolic phenotype, immune cell infiltration and inflammation was attenuated in the adipose tissue of obese {TPL2KO} mice coincident with reduced hepatic inflammatory gene expression and lipid accumulation. 
CONCLUSIONS Our results provide the first in vivo demonstration that {TPL2} ablation attenuates obesity-associated metabolic dysfunction. These data suggest {TPL2} is a novel target for improving the metabolic state associated with obesity.</style></abstract><notes><style face="normal" font="default" size="100%">{PMID:} 21346175</style></notes></record></records></xml>