RGD Reference Report - PI3Kgamma within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance. - Rat Genome Database

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PI3Kgamma within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance.

Authors: Becattini, B  Marone, R  Zani, F  Arsenijevic, D  Seydoux, J  Montani, JP  Dulloo, AG  Thorens, B  Preitner, F  Wymann, MP  Solinas, G 
Citation: Becattini B, etal., Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):E854-63. Epub 2011 Sep 26.
RGD ID: 6482700
Pubmed: PMID:21949398   (View Abstract at PubMed)
PMCID: PMC3198370   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1106698108   (Journal Full-text)

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 PI3Kgamma 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 PI3Kgamma 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 PI3Kgamma 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 PI3Kgamma action on diet-induced obesity depends on PI3Kgamma activity within a nonhematopoietic compartment, where it promotes energetic efficiency for fat mass gain. We also show that metabolic modulation by PI3Kgamma depends on its lipid kinase activity and might involve kinase-independent signaling. Thus, PI3Kgamma is an unexpected but promising drug target for the treatment of obesity and its complications.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
obesity  ISOPik3cg (Mus musculus)6482700; 6482700 RGD 
obesity  IMP 6482700 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma)

Genes (Mus musculus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)

Genes (Homo sapiens)
PIK3CG  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)


Additional Information