Background: Obesity-associated inflammation is characterized by an increased abundance of macrophages (MPhis) 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 MPhis and silence the cross-talk between human MPhis 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-kappaB) and activator protein-1 (AP-1), and induction of inflammatory genes in human MPhis (that is, differentiated U937 cells). In addition, we determined the effect of GPE pretreatment of MPhis on inflammation and insulin resistance in primary human adipocytes incubated with LPS-challenged MPhi-conditioned medium (MPhi-CM).
Methods and results: Pretreatment of MPhis with GPE attenuated LPS-induction of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1beta; chemokines, such as IL-8 and interferon-gamma 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-kappaB and AP-1 (c-Jun), as evidenced by decreased (1) phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38; (2) degradation of IkappaBalpha and activation of an NF-kappaB reporter construct; and (3) phosphorylation of c-Jun and Elk-1. Using LPS-challenged MPhi-CM, GPE pretreatment attenuated MPhi-mediated inflammatory gene expression, activation of an NF-kappaB reporter and suppression of insulin-stimulated glucose uptake in human adipocytes.
Conclusion: Collectively, these data demonstrate that GPE attenuates LPS-mediated inflammation in MPhis, possibly by decreasing the activation of MAPKs, NF-kappaB and AP-1, and that GPE decreases the capacity of LPS-stimulated MPhis to inflame adipocytes and cause insulin resistance.