Nutritionally mediated oxidative stress and inflammation

Abstract

There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NF κ B. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF- α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs) of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1 α , CCL4/MIP-1 β , CXCL2/MIP-2 α , and CXCL3/MIP-2 β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs) both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNF α , IL-1 β , and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

Figure 1

Downstream effects of nutrient overload. Overview of the downstream effects mediated by nutrient overload. Excess glucose and free fatty acids overwhelm the tricarboxylic acid (TCA) cycle which leads to an increase in the production of acetyl CoA. Excess acetyl CoA stimulates the mitochondria to produce excess superoxide in the electron transport chain, and the subsequent conversion of superoxide to hydrogen peroxide results in an increase of reactive oxygen species (ROS) within the cell. This change in redox status activates numerous redox-sensitive transcription factors, including NFκB, which is the main mediator of inflammatory responses.