Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes

Abstract

The increased generation of reactive oxygen species that occurs in the condition of obesity may be responsible for oxidative injury to erythrocyte membranes, which could lead to a decrease in tissue oxygenation. Therefore, we have looked into the effects of obesity on both indexes of oxidative damage and physical-chemical properties of erythrocyte membranes in 50 overweight or obese [25 Ͻ body mass index (BMI) Ͻ 33], normotensive, nondiabetic women and 50 age-matched lean healthy women (BMI Ͻ 25). In the obese group compared with the lean group, we found that a ) the onset of free radical-induced erythrocyte hemolysis and the ratio between reduced and oxidized glutathione were reduced, whereas the rate of free radicalinduced damage increased; b ) the n-3 fatty acid and the phospholipid contents decreased; c ) the ratio between cholesterol and phospholipids increased; and d ) the membrane fluidity decreased. These findings suggest an impairment of erythrocyte membrane physical-chemical properties in overweight and obese people as a consequence of oxidative injury that might be part of a pathogenetic mechanism responsible for obesity-related pathologies such as atherosclerosis and hypertension. -Cazzola, R., M. Rondanelli, S. Russo-Volpe, E. Ferrari, and B. Cestaro. Physiological oxidative metabolism and neutrophil activation occurring in the blood give rise to oxygen-reactive substances and other very active radical species that can irreversibly damage the surrounding macromolecules. In particular, these radicals can attack both the amino and thiol groups of proteins and the double bonds of polyunsaturated fatty acids in lipoproteins. Statistically significant correlations have been found between lipoprotein susceptibility to peroxidation, the degree of obesity, and the risk of developing cardiovascular disease (1). Because any increase in the rate of lipoprotein peroxidation not only diminishes their levels of polyunsaturated fatty acids but also consumes and reduces their antioxidant contents (vitamin E, ␤ -carotene, coenzyme Q, etc.), the consequence of these biochemical events in overweight and obese people is also a probable reduction of the "exchange rate" of both polyunsaturated fatty acids and lipophilic antioxidants that are normally transferred in the blood from the donor lipoproteins to the erythrocyte acceptor membranes. A decrease in both the degree of polyunsaturation of lipids and the antioxidant levels of the erythrocyte membrane could thus be expected, together with a decrease of both membrane fluidity and the activity of its membrane-bound enzymes. Because the erythrocyte membrane serves as a variable barrier to oxygen transport, the changes in its composition can induce cellular hypoxia in the tissue bed. Furthermore, because the size, shape, and diffusion capacity of a red blood cell depend on the structure of its membrane, alterations in membrane structure could lead to a decrease in tissue oxygenation (2). Such modifications of oxygen available in cardiovascular cells might be part ...

Increased glutathione conjugate transport: a possible compensatory protection mechanism against oxidative stress in obesity?

“…[29][30][31][32] It has also been shown that there is an obesity-related decrease in glutathione content of the erythrocytes. 7,8 In addition, Yoshida et al 33 reported that, in diabetes mellitus often accompanying obesity, GSH synthesis and conjugate transport are impaired in erythrocytes. However, this is the first study concerning the effects of obesity on the glutathione S-conjugate transport.…”

“…11,12 On the other hand, several investigators have shown that the levels of lipid peroxidation products were elevated in various tissues including blood in obesity. [36][37][38][39] It has been previously reported that transport systems for glutathione S-conjugates play significant roles in the biotransformation of toxic products arising from oxidative stress-induced lipid peroxidation, as well as various GSH S-conjugate with/which has mutagenic and carcinogenic activities. 16,17 Thus, it is of interest to see how glutathione conjugate transport in cells of obese can protect cells from CDNB-induced oxidative damage by exporting DNP-SG.…”

“…Alteration of membrane structure and fluidity has been established in obese subjects' erythrocytes. 36,47 It has also been previously reported that the various effects that are known to alter membrane fluidity altered the sensitivities of the regulation on the cell membrane transport, such as glucose transport and amino-acid transport. [48][49][50] Differences in membrane structure may be another explanation for the increase in DNP-SG transport of obese subjects.…”

“…Furthermore, previous studies have also reported that obese persons had lower concentrations of glutathione in erythrocytes. 7,8 Glutathione (g-glutamyl-cysteinyl-glycine, GSH) plays several functions in cells including the erythrocyte. It participates in the cellular defense system against oxidative stress by reducing disulfide linkage of proteins and other cellular molecules, is a substrate for reduction of hydrogen peroxide and organic peroxides by glutathione peroxidase, and is a substrate for glutathione S-transferase (GST)-catalyzed conjugation of many xenobiotics.…”

Membrane Level of Omega-3 Docosahexaenoic Acid Is Associated with Severity of Obstructive Sleep Apnea

“…Obesity is a risk factor for OSA, 38 and obesity has been associated with reduced RBC omega-3 status. 39 The latter relations are postulated to be secondary to increased peroxidation of RBC membrane FAs. It is thus possible that increased membrane FA oxidative damage could be a common thread tying together low omega-3 FA status, OSA, obesity, and CVD.…”