PI3Kγ activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity.

• The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in high-fat diet-induced inflammation and insulin resistance depended largely on its role in the control of adiposity, which was due to PI3Kγ activity in a nonhematopoietic cell type. However, PI3Kγ activity in leukocytes was required for efficient neutrophil recruitment to adipose tissue. Neutrophil recruitment was correlated with proinflammatory gene expression in macrophages in adipose tissue, which triggered insulin resistance early during the development of obesity. Our data challenge the concept that PI3Kγ is a general suppressor of classical macrophage activation and indicate that PI3Kγ controls macrophage gene expression by non-cell-autonomous mechanisms, the outcome of which is context-dependent.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Annan hälsovetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Other Health Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Adipose Tissue

pathology

Animals

Class Ib Phosphatidylinositol 3-Kinase

physiology

Diet

High-Fat

adverse effects

Gene Expression Profiling

Inflammation

etiology

prevention & control

Insulin Resistance

Leukocytes

enzymology

pathology

Lipid Metabolism

Macrophages

pathology

Male

Mice

Mice

Inbred C57BL

Mice

Knockout

Obesity

complications

physiopathology

Phosphorylation

Proto-Oncogene Proteins c-akt

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)