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Inhibition of phosphoinositide 3-kinase attenuates inflammation, obesity, and cardiovascular risk factors

机译:抑制磷酸阳性3-激酶衰减炎症,肥胖和心血管危险因素

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Phosphoinositide 3-kinase γ (PI3Kγ) plays a central role in inflammation, allergy, cardiovascular, and metabolic disease. Obesity is accompanied by chronic, low-grade inflammation. As PI3Kγ plays a major role in leukocyte recruitment, targeting of PI3Kγ has been considered to be a strategy for attenuating progression of obesity to insulin resistance and type 2 diabetes. Indeed, PI3Kγ null mice are protected from high fat diet–induced obesity, metabolic inflammation, fatty liver, and insulin resistance. The lean phenotype of the PI3Kγ-null mice has been linked to increased thermogenesis and energy expenditure. Surprisingly, the increase in fat mass and metabolic aberrations were not linked to PI3Kγ activity in the hematopoietic compartment. Thermogenesis and oxygen consumption are modulated by PI3Kγ lipid kinase–dependent and –independent signaling mechanisms. PI3Kγ signaling controls metabolic and inflammatory stress, and may provide an entry point for therapeutic strategies in metabolic disease, inflammation, and cardiovascular disease
机译:磷酸阳性3-激酶γ(PI3Kγ)在炎症,过敏,心血管和代谢疾病中起着核心作用。肥胖症伴有慢性低,低级炎症。由于PI3Kγ在白细胞募集中发挥着重要作用,因此PI3Kγ的靶向被认为是减轻肥胖进展到胰岛素抵抗和2型糖尿病的策略。实际上,PI3Kγ含氟小鼠免受高脂肪饮食诱导的肥胖,代谢炎症,脂肪肝和胰岛素抵抗的影响。 PI3Kγ-XULL小鼠的瘦表型已与增加的热生成和能量消耗相关联。令人惊讶的是,脂肪质量和代谢像差的增加与造血室中的PI3Kγ活性没有与PI3Kγ活性相关联。通过PI3Kγ脂质激酶依赖性和依赖性信号传导机构调节热生成和氧气消耗。 PI3Kγ信号传导控制代谢和炎症应激,并可为代谢疾病,炎症和心血管疾病中的治疗策略提供进入点

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