Polyphenol-rich grape powder extract (GPE) attenuates inflammation in human macrophages and in human adipocytes exposed to macrophage-conditioned media

Overman, A.; Bumrungpert, A.; Kennedy, A.; Martinez, K.; Chuang, C.-C.; West, T.; Dawson, B.; Jia, W.; McIntosh, M.
May 2010
International Journal of Obesity;May2010, Vol. 34 Issue 5, p800
Academic Journal
Background:Obesity-associated inflammation is characterized by an increased abundance of macrophages (MΦs) in white adipose tissue (WAT), leading to the production of inflammatory cytokines, chemokines and prostaglandins (PGs) that can cause insulin resistance. Grape powder extract (GPE) is rich in phenolic phytochemicals that possess anti-oxidant and anti-inflammatory properties.Objective:We examined the ability of GPE to prevent lipopolysaccharide (LPS)-mediated inflammation in human MΦs and silence the cross-talk between human MΦs and adipocytes.Design:We investigated the effect of GPE pretreatment on LPS-mediated activation of mitogen activated protein kinases (MAPKs), nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1), and induction of inflammatory genes in human MΦs (that is, differentiated U937 cells). In addition, we determined the effect of GPE pretreatment of MΦs on inflammation and insulin resistance in primary human adipocytes incubated with LPS-challenged MΦ-conditioned medium (MΦ-CM).Methods and Results:Pretreatment of MΦs with GPE attenuated LPS-induction of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β; chemokines, such as IL-8 and interferon-γ inducible protein-10 (IP-10); and a marker of PG production, cyclooxygenase-2 (COX-2). Grape powder extract also attenuated LPS activation of MAPKs, NF-κB and AP-1 (c-Jun), as evidenced by decreased (1) phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38; (2) degradation of IκBα and activation of an NF-κB reporter construct; and (3) phosphorylation of c-Jun and Elk-1. Using LPS-challenged MΦ-CM, GPE pretreatment attenuated MΦ-mediated inflammatory gene expression, activation of an NF-κB reporter and suppression of insulin-stimulated glucose uptake in human adipocytes.Conclusion:Collectively, these data demonstrate that GPE attenuates LPS-mediated inflammation in MΦs, possibly by decreasing the activation of MAPKs, NF-κB and AP-1, and that GPE decreases the capacity of LPS-stimulated MΦs to inflame adipocytes and cause insulin resistance.


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