Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling

Abstract

Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.

Fatty acid desaturase activity in mature red blood cells and implications for blood storage quality

“…Historically, RBCs have been reported to take up fatty acids from circulation and, as such, the fatty acyl composition of RBC membrane lipids closely mirrors that of plasma and is significantly modulated by dietary intervention (e.g., supplementation of n‐3 fatty acids) 3,4 . Factors such as exercise, 5–7 aging, 8–10 nutrition, 11,12 and diseases—from neurological disease 13 to cancer 14,15 —have all been associated with alterations of RBC membrane fatty acyl composition. Because RBCs are incapable of de novo synthesis of long‐chain fatty acids such as palmitate, 16 they do rely on an acyl‐carnitine system in equilibrium with high‐energy acyl‐CoAs for the repairing of damaged fatty acyl groups, 17 a pathway that is referred to as the Lands cycle.…”

Specialized interferon ligand action in COVID19

“…pyruvate, compare IFNL1 to IFNA1 in Figure 5G), as well as short chain fatty acids hexanoate and heptanoate, potentially indicative of dysregulation of mitochondrial metabolism in patients with high IFNL1. In RBCs, IFNL1 levels showed positive correlations with the levels of IDP (compare IFNL1 to IFNA6 in Figure 5 supplement 1E) and negative correlations with carnitine and acetyl-carnitine, potentially suggestive of RBC deformability issues (37,38) as a function of IFNL1 signaling. Plasma IFNA7 and IFNA10 (and to a lesser extent -IFNA1 and IFNA2) were positively associated with a cluster of acyl-carnitines (including octenoyl, dodecanoyl, dodecenoyl, hexadecenoyl-carnitine, compare IFNA10 to IFNA6 in Figure 5H), suggesting an association between these IFN ligands and altered fatty acid oxidation.…”

The Importance of Lipidomic Approach for Mapping and Exploring the Molecular Networks Underlying Physical Exercise: A Systematic Review

“…Thus, this systematic review provides an evaluation of 14 high-quality lipidomicsbased studies [13,[27][28][29][30][31][32][33][34][35][36][37][38][39] inquiring in depth about the exercise-induced changes of the human lipidome. Most of them (n = 10) [13,27,28,[30][31][32][33][37][38][39] regarded acute lipidome alterations following intense and prolonged exercise, while the other works (n = 4) [29,[34][35][36] focused on changes oncoming after a brief bout of acute exercise. Moreover, in 12 of these studies lipidomics was performed on biological fluids (blood and plasma); one was performed on skeletal muscle; and one collected both muscle biopsy and blood sample.…”

“…Lipidomic alterations in response to exercise depend on the differed cell types, and intensity and duration of effort. The main outcome measures included in this analysis (85.7%; n = 12) measured lipidomic responses through the use of liquid or gas chromatography mass spectrometry (LC-MS; GC-MS) [13,[27][28][29][30][31][32][33][34][35][36]38], ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) in one study [37] and nuclear magnetic resonance (NMR) for one study [39].…”

“…While these studies faced mainly the metabolic changes occurring in plasma, serum, or whole blood, only a few research studies have concentrated on metabolic modifications in red blood cells (RBCs) especially with regard to the type and level of physical exercise. Based on the assumption that erythrocytes represent the greatest part of circulating blood cells, Nemkov et al [38] hypothesized that the metabolic state of red blood cells would result in being correlated with endurance capacity. With a view to develop a greater comprehension of the metabolic environment related with changes in red blood cells in response to exercise, their research meant to evaluate the effects of high-intensity, prolonged physical exercise on concentrations of the lipid markers in various blood components.…”