Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance

• DOI: 10.1073/pnas.1016430108
• Publication Date: 2011-03-22T05:18:24Z
• Authors: Naoki Kobayashi; Kohjiro Ueki; Yukiko Okazaki; Aya Iwane; Naoto Kubota; Mitsuru Ohsugi; Motoharu Awazawa; Masatoshi Kobayashi; Takayoshi Sasako; Kazuma Kaneko; Miho Suzuki; Yoshitaka Nishikawa; Kazuo Hara; Kotaro Yoshimura; Isao Koshima; Susumu Goyama; Koji Murakami; Junko Sasaki; Ryozo Nagai; Mineo Kurokawa; Takehiko Sasaki; Takashi Kadowaki
• Keywords: Proinflammatory cytokine; Phosphoinositide 3-kinase

Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about role PI3Kγ obesity-induced tissues, systemic inflammation, development resistance. In present study, we used murine models both diet-induced genetically induced obesity to examine accumulation tissue macrophages Mice lacking p110γ ( Pik3cg −/− ), catalytic subunit PI3Kγ, exhibited improved sensitivity enhanced signaling tissues obese animals. livers mice, numbers infiltrated proinflammatory were markedly reduced, leading suppression reactions these Furthermore, bone marrow-specific deletion pharmacological blockade also ameliorated These data suggest plays crucial resistance can be therapeutic target for type 2 diabetes.