Université de Fribourg

PI3Kγ activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity

Breasson, Ludovic ; Becattini, Barbara ; Sardi, Claudia ; Molinaro, Angela ; Zani, Fabio ; Marone, Romina ; Botindari, Fabrizio ; Bousquenaud, Mélanie ; Rüegg, Curzio ; Wymann, Matthias P. ; Solinas, Giovanni

In: Science Signaling, 2017, vol. 10, no. 488, p. eaaf2969

The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in...

Université de Fribourg

JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage

Becattini, Barbara ; Zani, , Fabio ; Breasson, Ludovic ; Sardi, Claudia ; D'Agostino, Vito Giuseppe ; Choo, Min-Kyung ; Provenzani, Alessandro ; Park, Jin Mo ; Solinas, Giovanni

In: The FASEB Journal, 2016, vol. 30, no. 9, p. 3124–3132

Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its...

Université de Fribourg

PI3Kγ within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance

Becattini, Barbara ; Marone, Romina ; Zani, Fabio ; Arsenijevic, Denis ; Seydoux, Josiane ; Montani, Jean-Pierre ; Dulloo, Abdul G. ; Thorens, Bernard ; Preitner, Frédéric ; Wymann, Matthias P. ; Solinas, Giovanni

In: Proceedings of the National Academy of Sciences of the United States of America, 2011, vol. 108, no. 42, p. E854-E863

Obesity is associated with a chronic low-grade inflammation, and specific antiinflammatory interventions may be beneficial for the treatment of type 2 diabetes and other obesity-related diseases. The lipid kinase PI3Kγ is a central proinflammatory signal transducer that plays a major role in leukocyte chemotaxis, mast cell degranulation, and endothelial cell activation. It was also reported that...