脂肪生成
炎症
脂肪组织
下调和上调
内分泌学
内科学
脂肪细胞
白色脂肪组织
MAPK/ERK通路
生物
整合素
细胞生物学
受体
信号转导
医学
生物化学
基因
作者
Kyoung‐Jin Chung,Antonios Chatzigeorgiou,Matina Economopoulou,Rubén García‐Martín,Vasileia Ismini Alexaki,Ioannis Mitroulis,Marina Nati,Janine Gebler,Tjalf Ziemssen,Susan Goelz,Julia Phieler,Jin Ho Lim,Katia Karalis,Thalia Papayannopoulou,Matthias Blüher,George Hajishengallis,Triantafyllos Chavakis
摘要
Obesity is commonly accompanied by inflammatory responses in white adipose tissues. Chavakis and colleagues identify a vicious cycle involving α4 integrins and the adhesion molecule VCAM-1 that promotes inflammatory macrophage–adipocyte interactions and suppresses beige adipogenesis. In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α4 and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity. This adhesive interaction reciprocally and concomitantly modulated inflammatory activation of macrophages and downregulation of UCP1 expression dependent on the kinase Erk in adipocytes. Genetic or pharmacological inactivation of the integrin α4 in mice resulted in elevated expression of UCP1 and beige adipogenesis of subcutaneous AT in obesity. Our findings, established in both mouse systems and human systems, reveal a self-sustained cycle of inflammation-driven impairment of beige adipogenesis in obesity.
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