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

Becattini, Barbara and Marone, Romina and Zani, Fabio and Arsenijevic, Denis and Seydoux, Josiane and Montani, Jean-Pierre and Dulloo, Abdul G. and Thorens, Bernard and Preitner, Frédéric and Wymann, Matthias P. and Solinas, Giovanni. (2011) PI3Kγ within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance. Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, H. 42 , E854-E863.

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Official URL: http://edoc.unibas.ch/dok/A6004144

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Abstract

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 PI3K? 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 PI3K? activity within hematopoietic cells plays an important role in obesity-induced inflammation and insulin resistance. Here, we show that protection from insulin resistance, metabolic inflammation, and fatty liver in mice lacking functional PI3K? is largely consequent to their leaner phenotype. We also show that this phenotype is largely based on decreased fat gain, despite normal caloric intake, consequent to increased energy expenditure. Furthermore, our data show that PI3K? action on diet-induced obesity depends on PI3K? activity within a nonhematopoietic compartment, where it promotes energetic efficiency for fat mass gain. We also show that metabolic modulation by PI3K? depends on its lipid kinase activity and might involve kinase-independent signaling. Thus, PI3K? is an unexpected but promising drug target for the treatment of obesity and its complications.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Cancer- and Immunobiology (Wymann)
UniBasel Contributors:Wymann, Matthias P.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Variant title: PI3Kgamma within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance -- Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:27 Mar 2014 13:13

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