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Göteborgs universitets publikationer

PI3Kγ within a Nonhematopoietic Cell Type Negatively Regulates Diet-Induced Thermogenesis and Promotes Obesity and Insulin Resistance.

Författare och institution:
Barbara Becattini (Wallenberglaboratoriet); Romina Marone (-); Fabio Zan (-); Denis Arsenijevic (-); Josiane Seydoux (-); Jean-Pierre Montan (-); Abdul G. Dulloo (-); Bernard Thorens (-); Frédéric Preitner (-); Matthias P. Wymann (-); Giovanni Solinas (Institutionen för medicin, avdelningen för molekylär och klinisk medicin)
Publicerad i:
Proceedings of the National Academy of Science of the United States of America, 108 ( 42 ) s. E854–E863
Artikel, refereegranskad vetenskaplig
Sammanfattning (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 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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Obesity, Diabetes, Inflammation, Adiposity, Energy Balance, PI3K
Postens nummer:
Posten skapad:
2016-09-13 15:50

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