Solinas Giovanni, Becattini Barbara (2016), JNK at the crossroad of obesity, insulin resistance, and cell stress response, in Molecular Metabolism
Becattini B., Zani F., Breasson L., Sardi C., D'Agostino V. G., Choo M.-K., Provenzani A., Park J. M., Solinas G. (2016), JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage, in The FASEB Journal
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Marcelino Helena, Veyrat-Durebex Christelle, Summermatter Serge, Sarafian Delphine, Miles-Chan Jennifer, Arsenijevic Denis, Zani F, Montani Jean-Pierre, Seydoux Josiane, Solinas Giovanni, Rohner-Jeanrenaud Françoise, Dulloo Abdul (2013), A Role for Adipose Tissue De Novo Lipogenesis in Glucose Homeostasis During Catch-up Growth, in Diabetes
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Wymann Matthias, Solinas Giovanni (2013), Inhibition of phosphoinositide 3-kinase gamma attenuates inflammation, obesity, and cardiovascular risk factors, in Ann N Y Acad Sci.
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Zani Fabio, Breasson Ludovic, Becattini Barbara, Vukolic Ana, Montani Jean-Pierre, Albrecht Urs, Provenzani Alessandro, Ripperger Juergen A., Solinas Giovanni (2013), PER2 promotes glucose storage to liver glycogen during feeding and acute fasting by inducing Gys2 PTG and GL expression, in Molecular Metabolism
Solinas Giovanni (2012), Molecular pathways linking metabolic inflammation and thermogenesis., in Obesity Reviews
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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 (2011), PI3Kγ within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance., in Proceedings of the National Academy of Sciences of the United States of America
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The world epidemic of obesity is a major contributor to the global burden of several chronic diseases. Some diseases associated with obesity occur at a relatively early stage, such as insulin resistance and fatty liver, whereas others are associated with a longer exposure to obesity. Diseases associated with a chronic exposure to obesity include diabetes, non-alcoholic steato-hepatitis (NASH), liver fibrosis, cardiovascular diseases, and kidney dysfunctions. Most likely, the explosive raise of obesity among children will lead within the next decades to a proportional increase of the diseases associated with long-term exposure to obesity. Research aimed to understand the metabolic stress associated with obesity suggests that inflammation is an important pathogenic factor in obesity-induced glucose intolerance. Furthermore, the kinases IKKß and JNK1 were identified to be important molecular links between obesity, inflammation, and insulin resistance. Although several evidences indicate that specific anti-inflammatory interventions may be beneficial for the “early” metabolic derangements associated with obesity (eg. insulin resistance and fatty liver) it is not clear whether an anti-inflammatory therapy would be protective or safe over a longer period or at a more advanced stage of obesity related diseases (e.g. NASH). In this proposal we describe data suggesting a major role for the kinase PI3K? in diet-induced obesity, fatty liver, and insulin resistance. In this project we describe three studies: in the first one we propose to generate mice bearing a tissue-specific mutation at the PI3K? gene to specifically investigate the mechanism of PI3K? in diet-induced obesity, insulin resistance and fatty liver. The second study is aimed at investigating the role of PI3K? in a model of overt steatohepatitis and fibrosis. The aim of the third study is to explore the role the kinase PI3K? in the metabolic stress caused by prolonged exposure to high-fat obesogenic diet and in the associated metabolic dysfunctions. Overall we expect that the experiments here described will lead to a significant advancement of our understanding of the role of PI3K? in the pathogenesis of obesity-related diseases, and in particular insulin resistance and non alcoholic fatty liver disease.