Blocking CD40-TRAF6 Signaling is a Therapeutic Target in Obesity-Associated Insulin Resistance
Antonios Chatzigeorgiou;Tom Seijkens;Barbara Zarzycka;David Engel;Marjorie Poggi;Susan van den Berg;Sjoerd van den Berg;Oliver Soehnlein;Holger Winkels;Linda Beckers;Dirk Lievens;Ann Driessen;Pascal Kusters;Erik Biessen;Ruben Garcia-Martin;Anne Klotzsche-von Ameln;Marion Gijbels;Randolph Noelle;Louis Boon;Tilman Hackeng;Klaus-Martin Schulte;Aimin Xu;Gert Vriend;Sander Nabuurs;Kyoung-Jin Chung;Ko Willems van Dijk;Patrick Rensen;Norbert Gerdes;Menno de Winther;Norman Block;Andrew Schally;Christian Weber;Stefan Bornstein;Gerry Nicolaes;Triantafyllos Chavakis;Esther Lutgens
Abstract
Inflammation is a critical contributor to the pathogenesis of metabolic disorders associated with obesity. A group of molecules crucial in regulating the immune system are costimulatory molecules, including CD40. Our current study shows that CD40 acts as a double-edged sword in the metabolic syndrome through the initiation of differential signaling cascades. The CD40-TNF receptor-associated factor (TRAF) 2/3/5 signaling pathway protects against metabolic dysfunction and inflammation associated w