Investigation of time-dependent alterations in adipokine levels and endoplasmic reticulum stress markers in obese patients with laparoscopic sleeve gastrectomy.

BACKGROUND AND AIMS: We aimed to investigate the time-dependent alterations of serum, adipose tissue WISP1, Nrg4, asprosin, SPX adipokines and serum ER stress markers GRP78, XBP1, ATF6, CHOP in obese patients who underwent laparoscopic sleeve gastrectomy (LSG). MATERIALS AND METHODS: Morbidly obese patients (n = 19) and normal-weight individuals (n = 19) were compared. Preoperative (control, obese) and postoperative 1st, 3rd and 6th month (obese) follow-up measurements were obtained. Levels of adipokines, ER stress markers were measured with commercial kits. RESULTS: Body mass index (BMI), total fat, trunk fat mass, fat percentage of obese patients decreased after LSG. Postoperative serum glucose, insulin, HOMA-IR, triglyceride levels of obese patients decreased, HDL increased. In obese patients, preoperative LDL and total cholesterol, which were not different from control, were higher in the postoperative 6th month measurements. Omentum WISP1, subcutaneous adipose tissue WISP1 and SPX, and serum WISP1, asprosin, CHOP levels were higher, Nrg4 lower in obese patients. Serum Nrg4 was still lower in the postoperative 1st month measurements, while WISP1 was higher in the 3rd and asprosin in the 3rd, 6th months compared to control. 1st and 3rd month ATF6 and 3rd month CHOP concentrations were lower than preoperative values. Serum CHOP measured at the 6th month was significantly higher than control. Negative correlations were observed between serum Nrg4 and fat percentage, TG concentration. CHOP was negatively correlated with fat percentage. CONCLUSION: The correlations between changes in serum Nrg4, CHOP and fat percentage highlight the roles of Nrg4 and CHOP in the fat loss following LSG.

Exercise training and detraining process affects plasma adiponectin level in healthy and spontaneously hypertensive rats.

BACKGROUND: Adiponectin levels with long-term swimming exercise have been never investigated in spontaneously hypertensive rats (SHR). OBJECTIVE: This study was aimed to investigate the effects of exercise and detraining process on the adiponectin plasma levels of spontaneously hypertensive rats (SHR) and healthy Wistar-Kyoto rats (WKY). MATERIAL AND METHODS: The rats in the exercise groups were swimming for 10 weeks, 5 days/week, one hour in a day. The detraining rats were left to be sedentary in their cages for 5 weeks after 10 weeks of exercise period. RESULTS: The plasma adiponectin levels decreased in E and SHRE groups compared to the SC and the SHR groups, respectively. In addition, blood pressure was decreased in the exercise groups vs their controls. The adiponectin level was not found to be significantly different in ED and SHRED groups compared to their controls. The blood pressure did not differ between SDC and ED groups, although in the SHRED group it was found to be lower than in SHRSD group rats. CONCLUSION: The results of this study showed that exercise reduced plasma levels of adiponectin in healthy and spontaneously hypertensive rats. However, this difference disappeared at the end of the training processes. Our results suggest, that changes in plasma adiponectin levels are not responsible for changes in blood pressure (Tab. 2, Fig. 2, Ref. 43).

Vitamin E treatment enhances erythrocyte deformability in aged rats.

The harmful effects of aging on blood rheology have been well known. These effects in the aging have been found to be associated with an increase in oxidative stress. The aim of this study was to seek whether treatment of vitamin E as a potent antioxidant could improve the age-related haemorheological abnormalities. For this purpose, male Wistar rats at the age of 3 and 24 months were used. The following parameters were evaluated: red blood cell (RBC) deformability, aggregation, plasma viscosity, vitamin E level, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI), and the following results were obtained. First, aging was associated with a decrease in RBC deformability and increase in RBC aggregation and plasma viscosity. Second, compared with the young group, while plasma TOS levels and OSI were found to be significantly increased in aged rats, there was no significant change in their plasma TAS level. Third, vitamin E administration produced significant improvement in RBC deformability and decrement in TOS and OSI values in aged rats with respect to young and aged control groups. We did not find any significant effect of vitamin E treatment on RBC aggregation in both young and aged rats and finally, we found a significantly lower plasma vitamin E level in aged rats than in young rats. In conclusion, these findings suggest that blood rheology impairs with age and vitamin E has ameliorating effects on age-induced haemorheological abnormalities especially in RBC deformability, probably by reducing the increased oxidative stress in old age.

Exercise-induced oxidative stress affects erythrocytes in sedentary rats but not exercise-trained rats.

Oxidant stress is one of the factors proposed to be responsible for damaged erythrocytes observed during and after exercise. The impact of exertional oxidant stress after acute exhaustive treadmill running on erythrocyte damage was investigated in sedentary (Sed) and exercise-trained (ET) rats treated with or without antioxidant vitamins C and E. Exhaustive exercise led to statistically significant increments in the levels of thiobarbituric acid-reactive substance (TBARS) and H2O2-induced TBARS in Sed rats and resulted in functional and structural alterations in erythrocytes (plasma hemoglobin concentrations, methemoglobin levels, and rise in osmotic fragility of erythrocytes with decrease in erythrocyte deformability). Administration of antioxidant vitamin for 1 mo before exhaustive exercises prevented lipid peroxidation (TBARS, H2O2-induced TBARS) in Sed rats without any functional or structural alterations in erythrocytes. Parameters indicating erythrocyte lipid peroxidation and deterioration after exhaustive exercise in rats trained regularly with treadmill running for 1 mo were not different from those in Sed controls. Erythrocyte lipid peroxidation (TBARS) increased in exhausted-ET rats compared with ET controls; however, the plasma hemoglobin, methemoglobin levels, and erythrocyte osmotic fragility and deformability did not differ. Exhaustive exercise-induced lipid peroxidation in ET rats on antioxidant vitamin treatment was prevented, whereas functional and structural parameters of erythrocytes were not different from those of the ET controls. We conclude that exertional oxidant stress contributed to erythrocyte deterioration due to exercise in Sed but not in ET rats.

Red blood cell rheological alterations in hypertension induced by chronic inhibition of nitric oxide synthesis in rats.

Nitric oxide (NO) plays a major role in vascular regulation. Modulation of NO synthesis is known to influence blood pressure. Inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME; 72 mg/kg/day, p.o., 21 days) resulted in 60% increase in blood pressure in rats. Red blood cell (RBC) transit time measured by the cell transit analyzer increased significantly in the L-NAME treated group, in comparison to normotensive rats. RBC aggregation measured in autologous plasma, by a photometric rheoscope also increased significantly in the hypertensive rats. RBC cytosolic free calcium concentration was also significantly higher in the hypertensive animals. Incubation of RBC from hypertensive and control animals with NO donor, sodium nitroprusside (SNP; 10-1000 microM) for 60 minutes resulted in a dose-dependent decrease in RBC aggregation, however aggregation index was significantly higher in hypertensive group at each SNP concentration. Incubation with SNP had no effect on RBC deformability in the control group, while a slight decrease in RBC transit time was observed only at 10 microM SNP in the hypertensive group. These results imply that NO may play a role in the regulation of rheological properties of RBC and the alterations in these properties may at least in part be involved in the development of L-NAME induced hypertension.

Erythropoietin-induced rheological changes of rat erythrocytes.

The effects of recombinant human erythropoietin (rhEPO) on red blood cell (RBC) rheological properties were investigated in rats. Rats received intramuscular injections of 150 U/kg/d rhEPO for 5 d, following which blood samples were obtained 1, 5 or 10 d later. RBC deformability was assessed by determining cell transit times through 5-microm micropores (CTA) and RBC shape recovery time constants via photometry, aggregation in plasma and dextran was measured by photometry and RBC electrophoretic mobility was determined in a cylindrical electrophoresis system. RBC aggregation was found to be significantly decreased on day 5 after rhEPO treatment (P < 0.05), yet was unchanged from control on days 1 and 10. Mean RBC micropore transit times remained unchanged, but the distributions of transit times were altered; compared with control, the 5th percentiles on both days 1 and 5 were decreased and the 95th percentile on day 1 was elevated. Electrophoretic mobility of RBCs in phosphate-buffered saline was significantly increased on day 5 after rhEPO treatment (P < 0.05), with mobility measurements in dextran 500 (MW = 500 kDa) solutions suggesting that the cells' surface properties related to the formation of a 'depletion layer' may be altered on day 1. These results indicate that the rheological behaviour of RBC as a consequence of rhEPO treatment are temporal and are affected by the presence of reticulocytes as well as by the average age of the circulating cells.

Standard aggregating media to test the "aggregability" of rat red blood cells.

Rat red blood cells (RBC) exhibit low aggregation tendency in autologous plasma and in standard aggregating media (e.g., 3% Dextran 70; MW: 70 kD). In experimental studies performed on rats, 3% Dextran 70 was found to be an unsuitable suspending medium to test the "aggregability" of RBC in a standard medium. It has been observed that solutions of higher molecular weight polymers (i.e., dextran, MW: 500 kD; polyethylene glycol , MW: 35 kD; polyvinylpyrrolidone, MW: 360 kD), at low concentrations were strong aggregators for rat RBC. Among these polymer solutions 0.5% Dextran 500 and 0.75% polyvinylpyrrolidone 360 were found to be the most suitable suspending media, to distinguish between the aggregability of RBC from septic and control rats. Therefore, these two polymer solutions are recommended as the standard aggregating media for rat RBC, to test the RBC aggregability.

Effects of swimming exercise on red blood cell rheology in trained and untrained rats.

Red blood cell (RBC) mechanical properties were investigated after swimming exercise in trained and untrained rats. A group of rats was trained for 6 wk (60 min swimming, daily), and another group was kept sedentary. Blood samples were obtained either within 5 min or 24 h after 60 min swimming in both groups. In the untrained rats, the RBC aggregation index decreased to 2.60 +/- 0.4 immediately after exercise from a control value of 6.73 +/- 0.18 (P < 0.01), whereas it increased to 13.13 +/- 0.66 after 24 h (P < 0.01). RBC transit time through 5-microm pores increased to 3.53 +/- 0.16 ms within 5 min after the exercise from a control value of 2.19 +/- 0. 07 ms (P < 0.005). A very significant enhancement (166%) in RBC lipid peroxidation was detected only after 24 h. In the trained group, the alterations in all these parameters were attenuated; there was a slight, transient impairment in RBC deformability (transit time = 2.64 +/- 0.13 ms), and lipid peroxidation was found to be unchanged. These findings suggest that training can significantly limit the hemorheological alterations related to a given bout of exercise. Whether this effect is secondary to the training-induced reduction in the degree of metabolic and/or hormonal perturbation remains to be determined.

Aggregation behavior and electrophoretic mobility of red blood cells in various mammalian species.

Differences of red blood cell (RBC) aggregation among various mammalian species has been previously reported for whole blood, for RBC in autologous plasma, and for washed RBC re-suspended in polymer solutions. The latter observation implies the role of cellular factors, yet comparative studies of such factors are relatively limited. The present study thus investigated RBC aggregation and RBC electrophoretic mobility (EPM) for guinea pigs, rabbits, rats, humans and horses; RBC were re-suspended in isotonic 500 kDa dextran solutions for the EPM and aggregation measurements, with aggregation studies also done in autologous plasma. Salient results included: (1) species-specific RBC aggregation in both plasma and dextran (horse > human > rat > rabbit approximately = guinea pig) with a significant correlation between aggregation in the two media; (2) similar EPM values in PBS for rat, human and horse, a lower value for guinea pig, and a markedly reduced EPM for rabbit RBC; (3) EPM values in dextran with a rank order identical to that for cells in PBS; (4) relative EPM results indicating formation of a polymer-poor, low viscosity depletion layer at the RBC surface (greatest depletion for horse RBC). EPM-aggregation correlations were evident and generally consistent with the Depletion Model for aggregation, yet did not fully explain differences between species; additional studies at various ionic strengths and with various dextran fractions thus seem warranted.