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

Détails

ID Serval
serval:BIB_F18D7780E975
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PI3Kγ within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Becattini B., Marone R., Zani F., Arsenijevic D., Seydoux J., Montani J.P., Dulloo A.G., Thorens B., Preitner F., Wymann M.P., Solinas G.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2011
Volume
108
Numéro
42
Pages
E854-E863
Langue
anglais
Résumé
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 PI3Kγ 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 PI3Kγ 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 PI3Kγ action on diet-induced obesity depends on PI3Kγ activity within a nonhematopoietic compartment, where it promotes energetic efficiency for fat mass gain. We also show that metabolic modulation by PI3Kγ depends on its lipid kinase activity and might involve kinase-independent signaling. Thus, PI3Kγ is an unexpected but promising drug target for the treatment of obesity and its complications.
Mots-clé
Adipose Tissue, White/enzymology, Animals, Class Ib Phosphatidylinositol 3-Kinase/deficiency, Class Ib Phosphatidylinositol 3-Kinase/genetics, Diet, High-Fat/adverse effects, Fatty Liver/enzymology, Fatty Liver/etiology, Inflammation/enzymology, Insulin Resistance/physiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, Obesity/enzymology, Obesity/etiology, Phenotype, RNA, Messenger/genetics, RNA, Messenger/metabolism, Signal Transduction, Sterol Esterase/metabolism, Thermogenesis/physiology, Thinness/enzymology
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/10/2011 11:31
Dernière modification de la notice
09/05/2019 3:19
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