Genes Involved in Oxidative Stress Pathways Are Differentially Expressed in Circulating Mononuclear Cells Derived From Obese Insulin-Resistant and Lean Insulin-Sensitive Individuals Following a Single Mixed-Meal Challenge

Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases. Introduction Oxidative stress, resulting from an overproduction of oxidants (free radicals or other reactive species) and/or reduced antioxidant activity in cells and plasma, can contribute to impaired insulin signaling (1–4). Oxidative stress occurs early in the development of nutritional excess-induced insulin resistance in healthy men (5, 6). Oxidation of excess nutrients increases mitochondrial formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) (7). The resultant oxidative stress might induce deleterious changes in macromolecules such as DNA, proteins, and lipids. In addition, a number of stress-sensitive pathways including p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), or inhibitor of NF-κB kinase (IκKβ) are activated (8). These pathways, in turn, impede insulin signaling and glucose transport activity, leading to insulin resistance which is associated w...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research