- Macronutrient intake induces oxidative and inflammatory stress while insulin causes suppression of reactive oxygen species generation and inflamamtion
Paresh Dandona, Kaleida Health, Buffalo, NY, USA
Following our original observation that the intake of 75g of glucose in normal subjects induces an increase in ROS generation by mononuclear cells (MNC), we have shown that glucose, equi- caloric amounts of fat (eaten as cream) and a mixed fast food meal (900 calories) induce not only an increase in ROS generation by MNC but also cause an increase in p47 phox expression. In addi- tion, there is an increase in intranuclear NF B binding, a fall in IkB expression and an increase in IKK and IKK expression. There is a concomitant increase in TNFa mRNA in the MNC. Two other pro-inflammatory transcription factors, activator protein-1 (AP-1) and early growth response-1 (Egr-1), were also induced by glucose intake. There was an increase in MMP-2, MMP-9, tissue factor (TF) and PAI-1. Thus, there occurs a comprehensive oxida- tive and inflammatory stress response following macronutrient in- take. Consistent with this concept, the state of obesity, associated with increased macronutrient intake, is characterized by an in- crease in oxidative stress and chronic low grade inflammation. As would be expected, caloric restriction in the obese results in a marked reduction in ROS generation by MNC and other indices of oxidative stress, like lipid peroxidation and protein carbonylation. A 48 hour fast in normal subjects leads to a reduction in ROS gen- eration by 50% and a parallel reduction in p47phox. In contrast to macronutrient intake, a low dose insulin infusion (2 units per hour), results in a significant reduction in ROS generation by MNC, p47phox expression, intranuclear NF B binding with an in- crease in IkB expression. In addition, there is a suppression of AP-1 and Egr-1, MMP-2, MMP-9, PAI-1 and tissue factor (TF). This allows us to conclude that there exists a novel relationship between macronutrient intake and insulin, the hormone secreted in response to macronutrient intake.