Procedure

Following the previous evaluation, all patients will be divided randomly into the following groups: The training group (Group A) received aerobic exercise training for 6 months on the treadmill (EnrafNonium, Model display panel Standard, NR 1475.801, Holand) which was conducted according to recommendation of aerobic exercise application approved by the American College of Sports Medicine [28]. Training program will include 5 minutes for warming–up in the form of range motion and stretching exercises , 30 minutes of aerobic exercise training with intensity equal 60-70% of the individual maximum heart rate followed by cooling down for 10 minutes (on treadmill with low speed and without inclination). Participants had 3 sessions /week for 6 months with close supervision of physical therapist. Also, a dietician performed an interview-based food survey for all participants of group (A) for detection of feeding habits, abnormal dietary behavior and to prescribe the balanced low caloric diet [29] that provided 1200Kilocalories/ day for 6 months. The same dietitian continuously monitored all participant caloric intakes through reviewing the detailed record of food intake every 2 weeks [30,31]. The control group (Group B) received no exercise intervention or diet regimen.

Statistical Analysis

The mean values of the investigated parameters obtained before and after three months in both groups were compared using paired “t” test. Independent “t” test was used for the comparison between the two groups (P<0.05)..

Results

Sixty obese patients with NASH completed the screening evaluation and underwent randomization. The baseline characteristics of the patients who underwent randomization, none of the baseline characteristics differed significantly between the two groups as listed in Table 1.

The mean values of body mass index (BMI), TNF-α, IL-6, conjugated dienes (CD) and malondialdehyde (MDA) were significantly decreased, while the mean values of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH) were significantly increased in patients of group (A) (Table 2), while changes were not significant in group (B) (Table 3). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study (Table 4).

BMI: Body Mass Index; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; HOMA-IR: Homeostasis Model Assessment-Insulin Resistance Index; HDL-c: High Density Lipoprotein Cholesterol; LDL-c: Low Density Lipoprotein Cholesterol; AST: Aspartate Aminotransferase; ALT: Alanine Aminotransferase

BMI: Body Mass Index; TNF-α: Tumor Necrosis Factor -alpha; IL-6: Interleukin-6; CD: Conjugated Dienes; MDA: Malondialdehyde; GPx: Glutathione Peroxidase; SOD: Superoxide Dismutase; GSH: Glutathione;

*Significant level (p<0.05).

BMI: Body Mass Index; TNF- α: Tumor Necrosis Factor -Alpha; IL-6: Interleukin-6; CD: Conjugated Dienes; MDA: Malondialdehyde; GPx: Glutathione Peroxidase; SOD: Superoxide Dismutase; GSH: Glutathione.

BMI: Body Mass Index; TNF- α: Tumor Necrosis Factor -Alpha; IL-6: Interleukin-6; CD: Conjugated Dienes; MDA: Malondialdehyde; GPx: Glutathione Peroxidase; SOD: Superoxide Dismutase; GSH: Glutathione;

*Significant level (p<0.05).

Discussion

Non-alcoholic steatohepatitis (NASH) can lead to advanced fibrosis, hepatocellular carcinoma, and end-stage liver disease requiring liver transplantation [32]. Oxidative stress (OS) caused by reactive oxygen species is, however, known to be of major importance in the progression of this disease [33]. As oxidative stress (OS) seems to be the major factor in the disease, it is clear that by blocking OS, the disease could be halted. Therefore this study aimed to examine effects of 6 months weight reducing program on inflammatory cytokines and oxidative stress markers among obese Saudi patients with non-alcoholic steatohepatitis. The main finding of the present study was that weight reducing program ameliorated inflammatory cytokines (TNF-α and IL-6) and markers of oxidative and anti-oxidative stress (MDA, CD, CPX, GSH and SOD) in obese patients with NASH as a result of weight loss, these results are in line with many previous studies.

Results of our study agreed with Dandona et al. [34] who reported that weight loss reduces TNF-α in obese. Also, Sandoval and Davis approved that patients who had bariatric surgery gained reduction in IL-6 concentration and improved insulin sensitivity in parallel to weight loss [35]. Also, Balagopal et al. [36] reported that obese adolescents who underwent a 3-month lifestyle intervention of enhanced physical activity and nutrition habits had decreased body fat percentage, insulin resistance and IL-6. Likewise, Sheu et al. [37] reported that 5% of body weight loss obtained after 12 weeks of caloric restriction and exercises resulted in significant reduction in TNF-α and IL-6 of obese women. Selvin et al. [38] clearly stated that in their systemic review that weight loss was associated with a decrease in sCRP in these subjects and related to the amount of weight loss. Moreover, You and Nicklas &Nicklas and colleagues stated that weight loss leads to reductions in circulating IL-6, TNF-α and CRP levels regardless of the way in which the weight loss was achieved, including hypocaloric dietary intake, exercise, or liposuction [39,40]. Lang et al. [41] established that a weightreducing program had anti-atherogenic and inflammatory effects in their study on three obese men and eleven obese women for eight weeks. The three possible mecha¬nisms of exercise antiinflammatory effects include reduction in visceral fat mass [42]; reduction in the circu¬lating numbers of pro-inflammatory monocytes [43] and an increase in the circulating numbers of regulatory T cells [44].

Concerning the markers of oxidative and anti-oxidative stress, the observation in this study indicated a significant reduction in MDA& CD and increased in CPX, GSH and SOD as a result of weight loss at the end of the study. Nevertheless, the current data are in line with one previous study by Roberts et al. [45] Proved that after three weeks of combination between diet and exercise there was a significant reduction in BMI, lipid profile, fasting blood sugar, C-reactive protein and insulin homeostasis which ameliorates oxidative stress, inflammation and monocytes-endothelial interaction among diabetic patients. However, retrospective data from 169 obese, middle-aged men who were enrolled in a 12-week weight reduction program through lifestyle modification consisting of dietary restriction plus aerobic exercise showed significant decrease in lipid peroxidation and a significant increase in adiponectin level [24].

The possible mechanism for modulation of the oxidative stress markers induced by weight reduction could be due to reverse the mechanism by which obesity produces oxidative stress, which include reverse of mitochondrial and peroxisomal oxidation of fatty acids along with reduction of over-consumption of oxygen that generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria [46].

Conclusion

Weight loss ameliorates inflammatory cytokines and oxidative stress markers in obese patients with NASH.

Acknowledgment

The author is grateful for Prof. Shehab M. Abd El-Kader, professor of physical therapy for his kind help in clamp procedures of this article.

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