High Fat Diets Impair Body's Antioxidant System Leading to Chronic Inflammation!

As you know, I have suggested that deficiencies in the Nrf2 pathway may lead to any number of conditions where oxidative stress is a factor. Just a few of these are chronic fatigue syndrome, fibromyalgia, cardiovascular disease and diabetes. As we have described before, the Nrf2 pathway includes a number of proteins that form the natural antioxidant system. Its main purpose is to neutralize reactive species that are formed from metabolic processes to avoid damage to cells and tissue. Nrf2 is conserved in many tissues and developed as a means to deal with aerobic metabolism. In the past, we have also discussed how many factors can effect its expression such as TNF-a, microRNa, methylation, hyperglycemia, hypertension and high-fat diets.

I like to take a systems approach when discussing the Nrf2 pathway, disease and provide information from a variety of sources. With this in mind, I want to address some key points that one author made about selenium deficiency and high-fat diets and their impact on the Nrf2 pathway in swine. Please note, physiological conditions in animals do not present exactly like they do in humans. However, there is much to be learned about human disease by studying them in different animal species. On the other hand, sometimes it is just more practical.

The following are just a few of the observations Yang made in pigs fed a selenium deficient, high-fat diet.

1. neutrophil phagocytosis was impaired.
2. significant generation of ROS and increase in oxidative stress
3. heat shock protein mRNA significantly elevated
4. altered levels of selenoproteins than the control
5. lower levels of Nrf2 and downstream target genes
6. increased levels of inflammatory cytokines Tnf-a and Il-1b
7. increase in mRNA of iNos, Il-6, NF-kb and others
8. decrease in anti-inflammatory cytokines
9. macrophage infiltration in adipose tissue resulting in changes in inflammatory cytokines

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Oxidative stress induced by Se-deficient high-energy diet implicates neutrophil dysfunction via Nrf2 pathway suppression in swine. Oncotarget, Vol. 8, No. 8. (21 February 2017), pp. 13428-13439 by Tianshu Yang, Zeping Zhao, Tianqi Liu, et al.