Role of Endoplasmic Reticulum and Oxidative Stress Parameters in the Pathophysiology of Disease-Related Malnutrition in Leukocytes of an Outpatient Population

Abstract

Cellular pathways such as inflammation or oxidative stress are the cause and triggers of disease-related malnutrition (DRM), but the influence of these markers on endoplasmic reticulum (ER) stress is unknown. The objective of this study was to analyze the relationship between mitochondrial function and ER stress parameters in a DRM population. The study population was composed of 82 outpatient subjects, of whom 45 were diagnosed with DRM and 37 were confirmed to be normonourished according to the American Society for Parenteral and Enteral Nutrition ASPEN criteria. We evaluated anthropometrical and biochemical parameters, pro-inflammatory cytokines in serum. Oxidative and ER stress markers were analyzed in leukocytes. DRM patients showed significant reductions in albumin and transferrin concerning the normonourished group, and also displayed higher levels of hsCRP, IL6, and TNFα, and the soluble adhesion molecules VCAM-1 and ICAM-1. Besides, oxygen consumption and mitochondrial membrane potential were reduced and Radical Oxygen Species ROS production was enhanced in DRM patients. In the case of ER markers, protein and mRNA expression revealed that CHOP, ATF6, and the P-eIF2α signal were enhanced in malnourished patients compared to control subjects. Correlation studies supported a relationship between weight loss and increased inflammation, mitochondrial dysfunction, and compromised function of the ER. Our results demonstrate that ER stress signaling pathways are influenced by inflammation and mitochondrial function in the leukocytes of a DRM population.

Circulating mtDNA and Impaired Intestinal Barrier after Gastrointestinal Surgery Are Correlated with Postoperative SIRS

“…Some studies have found increased inflammatory responses in patients with disease-related malnutrition [ 33 ], and our study observed a similar phenomenon. That is, both albumin and prealbumin showed a decreasing trend after surgery.…”

Role of Autophagy and Apoptosis in Aluminum Exposure-Induced Liver Injury in Rats

“…It can promote the formation of reactive oxygen species (ROS), improve the oxidation level and reduce the function of the antioxidant defense system and induce the oxidative stress response in cells [24]. Moreover, ROS can also lead to endoplasmic reticulum stress and mitochondrial dysfunction through a series of pathways [25]. It has been reported that oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress can eventually induce abnormal autophagy or excessive apoptosis, thus damaging cells and tissues and further affecting their biological activities [26][27][28].…”

Physical Exercise Decreases Endoplasmic Reticulum Stress in Central and Peripheral Tissues of Rodents: A Systematic Review

“…ER is formed from plasma membrane invaginations and is involved in several functions, including the biosynthesis of lipids and proteins and their storage, as well as regulating enzyme activity and metabolism [ 2 , 3 ]. Under conditions of cellular stress (e.g., malnutrition, overnutrition, and physical inactivity), ER induces an increase in the level of unfolded proteins [ 4 , 5 , 6 ]. The accumulation of unfolded proteins in ER lumen is responsible for triggering an unfolded protein response (UPR), which promotes morphophysiological changes capable of generating ER stress [ 7 ].…”

“…Under conditions of cellular stress (e.g., malnutrition, overnutrition, and physical inactivity), ER induces an increase in the level of unfolded proteins [4][5][6]. The accumulation of unfolded proteins in ER lumen is responsible for triggering an unfolded protein response (UPR), which promotes morphophysiological changes capable of generating ER stress [7].…”