HM-chromanone attenuates TNF-α-mediated inflammation and insulin resistance by controlling JNK activation and NF-κB pathway in 3T3-L1 adipocytes

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 & PRIME;-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)-alpha-mediated inflammation and insulin resistance in 3T3-L1 adipocytes. TNF-alpha triggers the release of inflammatory cytokines and activation of the mitogen-activated protein kinase and nuclear factor (NF)-kappa B signaling pathways. In this study, HM-chromanone inhibited the production of inflammatory cytokines and chemokines [TNF-alpha, interleukin (IL)-6, IL-1 beta, and monocyte chemoattractant protein 1] involved in inflammation and insulin resistance. Furthermore, TNF-alpha treatment increased c-Jun-NH2 terminal kinase (JNK) phosphorylation, whereas HM-chromanone significantly decreased JNK phosphorylation in a dose-dependent manner. TNF-alpha treatment increased the activation of inhibitor kappa B (I kappa B) kinase (IKK), I kappa B alpha, and NF-kappa Bp65 compared with that of the control. However, HM-chromanone significantly blocked IKK, I kappa B alpha, and NF-kappa Bp65 activation. Upon adipocyte stimulation with TNF-alpha, 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-alpha-mediated inflammation and insulin resistance by regulating JNK activation and the NF-kappa B 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.