Tomato extract suppresses the production of proinflammatory mediators induced by interaction between adipocytes and macrophages.

Obese adipose tissue is characterized by enhanced macrophage infiltration. A loop involving monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNFα) between adipocytes and macrophages establishes a vicious cycle that augments inflammatory changes and insulin resistance in obese adipose tissue. Tomatoes, one of the most popular crops worldwide, contain many beneficial phytochemicals that improve obesity-related diseases such as diabetes. Some of them have also been reported to have anti-inflammatory properties. In this study, we focused on the potential protective effects of phytochemicals in tomatoes on inflammation. We screened fractions of tomato extract using nitric oxide (NO) assay in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. One fraction, RF52, significantly inhibited NO production in LPS-stimulated RAW264 macrophages. Furthermore, RF52 significantly decreased MCP-1 and TNFα productions. The coculture of 3T3-L1 adipocytes and RAW264 macrophages markedly enhanced MCP-1, TNFα, and NO productions compared with the control cultures; however, the treatment with RF52 inhibited the production of these proinflammatory mediators. These results suggest that RF52 from tomatoes may have the potential to suppress inflammation by inhibiting the production of NO or proinflammatory cytokines during the interaction between adipocytes and macrophages.

Auraptene suppresses inflammatory responses in activated RAW264 macrophages by inhibiting p38 mitogen-activated protein kinase activation.

SCOPE: Inflammation plays a key role in obesity-related pathologies such as insulin resistance and type 2 diabetes. Hypertrophied adipocytes trigger the enhancement of macrophage infiltration and the release of various proinflammatory factors in obese adipose tissue. In this study, we examined whether auraptene, a citrus-fruit-derived compound, could suppress the production of inflammatory factors that mediate the interaction between adipocytes and macrophages. METHODS AND RESULTS: Experiments using a co-culture system of 3T3-L1 adipocytes and RAW264 macrophages showed that auraptene reduced the production of nitric oxide and tumor necrosis factor-α. In RAW264 macrophages, auraptene also suppressed the inflammation induced by either LPS or the conditioned medium derived from 3T3-L1 adipocytes. In addition, auraptene inhibited the phosphorylation of the p38 mitogen-activated protein kinase and suppressed the production of proinflammatory mediators in activated macrophages. CONCLUSION: Our findings indicate that auraptene exhibits anti-inflammatory properties by suppressing the production of inflammatory factors that mediate the interaction between adipocytes and macrophages, suggesting that auraptene is a valuable food-derived compound with a potential to attenuate chronic inflammation in adipose tissue and to improve obesity-related insulin resistance.