胰岛素抵抗
肿瘤坏死因子α
炎症
磷酸化
IκB激酶
内科学
内分泌学
激酶
胰岛素受体
IRS1
促炎细胞因子
化学
NF-κB
胰岛素
生物
医学
生物化学
作者
Jea Eun Park,Eunji Kang,Jiarui Han
标识
DOI:10.1016/j.ejphar.2022.174884
摘要
Obesity is a major public health problem worldwide and causes inflammation and insulin resistance in adipose tissue. We investigated the ability of (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (HM-chromanone) isolated from Portulaca oleracea to attenuate the activation of inflammatory cytokines and signaling pathways associated with tumor necrosis factor (TNF)-α-mediated inflammation and insulin resistance in 3T3-L1 adipocytes. TNF-α triggers the release of inflammatory cytokines and activation of the mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathways. In this study, HM-chromanone inhibited the production of inflammatory cytokines and chemokines [TNF-α, interleukin (IL)-6, IL-1β, and monocyte chemoattractant protein 1] involved in inflammation and insulin resistance. Furthermore, TNF-α treatment increased c-Jun-NH2 terminal kinase (JNK) phosphorylation, whereas HM-chromanone significantly decreased JNK phosphorylation in a dose-dependent manner. TNF-α treatment increased the activation of inhibitor kappa B (IκB) kinase (IKK), IκBα, and NF-κBp65 compared with that of the control. However, HM-chromanone significantly blocked IKK, IκBα, and NF-κBp65 activation. Upon adipocyte stimulation with TNF-α, phosphorylated insulin receptor substrate (pIRS)-1 serine 307 levels increased and pIRS-1 tyrosine 612 levels decreased compared with those of the control. Upon treatment with HM-chromanone, serine 307 phosphorylation of IRS-1 was inhibited and tyrosine 612 phosphorylation of IRS-1 was increased. Thus, HM-chromanone improved TNF-α-mediated inflammation and insulin resistance by regulating JNK activation and the NF-κB pathway, thereby reducing inflammatory cytokine secretion and inhibiting serine phosphorylation of IRS-1 in the insulin signaling pathway. These results suggest the potential of HM-chromanone to improve inflammatory conditions and insulin resistance in adipocytes.
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