Impact of aerobic versus resisted exercise training on systemic inflammation biomarkers and quality of Life among obese post-menopausal women

Background Although post-menopausal obesity is an important public national health problem in Saudi Arabia, to date no study has evaluated the effects of weight reduction on biochemical & clinical parameters and quality of Life for obese Saudi post-menopausal women. Objective The aim of this study was examine the effects of aerobic versus resisted exercise training effects upon systemic inflammation biomarkers and quality of life for obese post-menopausal Saudi women. Material and Methods One hundred Saudi post-menopausal obese women participated in this study, their age ranged from 50–58 years and their body mass index (BMI) ranged from 30–35 kg/m2. All participants were divided into two equal groups: The first group received aerobic exercise training on treadmill where, the second group received resisted exercise training. Health-related quality of life (SF-36 HRQL), tumor necrosis factor- alpha(TNF-α), Interleukin-2(IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6) and C-reactive protein (CRP) were measured before and after 3 months at the end of the study. Results The mean values of SF-36 HRQL subscale scores were significantly increased, while the mean value of TNF-α, Il-2, IL-4, IL-6, CRP and BMI were significantly decreased in both groups after treatments. There were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment with more changes in patients received aerobic exercise training. Conclusion The current study provides evidence that aerobic exercise is more appropriate than resisted exercise training in modulating inflammatory cytokines and quality of life among obese post-menopausal women.


Introduction
Post-menopausal women, especially those with body mass index (BMI) greater than 30 kg/m2, have lower health-related quality of life (HRQOL) in physical functioning, energy, and vitality compared with normal-weight women 1 . Nearly two-thirds of American adults are overweight or obese 2 . The current epidemic of overweight and obesity is one of the major public health concerns worldwide 3 . The prevalence of overweight and obesity has increased significantly over the past 30 years, with overweight and obesity now affecting 1.5 billion adults globally 4 . Worldwide, 2.8 million people die each year of obesity-related diseases, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and metabolic syndrome 5 . Obesity may significantly reduce HRQOL. A review of 8 studies examining HROQL among women aged over 55 years old concluded that post-menopausal women, especially those with BMI greater than 30 kg/m2, have lower HRQOL in physical functioning, energy, and vitality compared with normal-weight women1. Obesity impacts a variety of dimensions of quality of life, including vitality, bodily pain, and even social functioning. Obese individuals report significantly lower HRQL than nor-mal-weight individuals 6 . General health problems, mobility/functional disability, depression and low self-esteem are commonly reported among obese subjects 7 .
Quality of life (QoL) in post-menopausal women may be compromised as a consequence of climacteric symptoms associated to psychosocial and cultural determinants 8 . There is a growing demand for health care proposals aimed at menopausal women and looking to promote a healthier female aging process and with a better QoL 9 . Hormone replacement therapy (HRT) has been indicated to minimize menopausal symptoms; however there are controversies as to whether its effects improve QoL. There are still some questions regarding the risks and benefits of HRT in post-menopausal women 10,11 .
Aerobic exercise training is an effective and cost-efficient alternative therapy for disorders of anxiety and mood disorders 12 . Also, exercise training slow down the progression of cognitive decline 13 , improves performance on tests of cognition and psychological wellbeing 14 and enhances sleep quality 15 . However, the available previous studies involving the impact of exercise training upon the quality of life, psychological wellbeing along with systemic inflammation in post-menopausal women is limited in number 16 .
As the ideal exercise intensity that efficiently modulates the elevated inflammatory cytokines and abnormal HRQOL among obese post-menopausal women is inconclusive, this study was designed to compare the impact of aerobic versus resisted exercises on inflammatory cytokines and HRQOL in obese post-menopausal women.

Patients and methods Subjects
One-hundred Saudi post-menopausal obese women participated in this study, their age ranged from 50-58 years and their BMI ranged from 30-35 kg/m2. All volunteers were asked to read and sign an informed consent document prior to participation. Women who were smokers, having any endocrine, musculoskeletal, renal, liver, cardiac disorders, diabetes and chest diseases were excluded. Participants were assigned into 2 groups; group (A) received aerobic exercise training for 3 months and group (B) received resisted exercise training. The CONSORT diagram outlining the details of the screening, run-in and randomization phases of the study and reasons for participant exclusion can be found in figure (1). Informed consent was obtained from all participants. This study was approved by the Scientific Research Ethical Committee, Faculty of Applied Medical Sciences at King University. The SF-36 included eight subscales: Vitality, Bodily Pain, General Health, Physical Functioning, Social Functioning, Physical Role Functioning, Emotional Role Functioning, and Mental Health. In addition to these subscales, the SF-36 also included a question asking participants to report the amount of change in their general health over the past year referred to as health transition 17 . 2. Biochemical analyses: Blood samples were drained from the antecubital vein after a 12-h fasting, the blood samples were centrifuged at + 4 °C (1000 = g for 10 min). Interleukin-2 (IL-2) Interleukin-4 (IL-4), Interleukin-6 (IL-6) levels were analyzed by "Immulite 2000" immunassay analyzer (Siemens Healthcare Diagnostics, Deerfield, USA). However, tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) levels were measured by ELISA kits (ELX 50) in addition to ELISA microplate reader (ELX 808; BioTek Instruments, USA). Measurements of TNF-α, Il-2, IL-4, IL-6 and CRP were taken before starting of the study (pre-test) and after 12 weeks (post-test). All measurements were taken before the starting of the study (pre-test) and after three months at the end of the study (post-test).

Procedures
Following the previous evaluation ,all participants were assigned into two groups: 1. Group (A) participated in a treadmill aerobic exercise (Enraf Nonium, 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 18 . Training program was included five minutes for warming -up in the form of range motion and stretching exercises , thirty minutes of aerobic exercise training ( 60-70% of maximum heart rate) and five minutes of cooling down (on treadmill with low speed and without inclination). Participants had three sessions /week for 3 months with close supervision of physical therapist.
2. Group (B) participated in the resistance exercises on some resistance gym machines (Nautilus Sports/Medical Industries, Independence, VA), three sessions of resistance exercise training /week for 3 months. Each session of resistance training program included five minutes for warming -up in the form of range motion and stretching exercises, 30 minutes of resistance exercise training and 5 minutes of cooling down 19 .

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). Table 1 shows the baseline characteristics of the participants who entered the trial. There was no significant differences in baseline characteristics between the two groups were found. The mean values of SF-36 HRQL subscale scores and 6MWT were significantly increased, while the mean value of TNF-α, Il-2, IL-4, IL-6, CRP and BMI were significantly decreased in both groups after treatments ( Tables  2-5). There were significant differences between mean levels of the investigated parameters of group (A) and group (B) after treatment with more changes in patients received aerobic exercise training (Tables 6 and 7). These results confirm that aerobic exercise is more appropriate than resisted exercise training in modulating inflammatory cytokines and quality of life among obese post-menopausal women.     CRP: C-reactive protein, (*) indicates a significant difference between the two groups, P < 0.05.

Discussion
Regular physical activity may attenuate post-menopausal symptoms related to physical and behavioral changes, positively influencing QOL 9,11,20 . However, studies on the effects of aerobic exercises alone are found in literature 11,21 . The fact that resisted exercise enhances muscle strength 22 and body composition 23 is well established, but the association of resisted exercise to QOL improvement has not been demonstrated. Therefore, the aim of this study was to examine the effects of aerobic versus resist- The results of our study regarding the QOL proved that both aerobic and resisted exercise training group improved mean values of SF-36 subscale scores in obese post-menopausal women. In addition, there was a significant difference between both groups at the end of the study with more reduction of group (A) received aerobic exercise training. Our findings were consistent with several studies have shown that exercise intervention might enhance health-related quality of life and psychological well-being 24-31 as Teomana et al. enrolled 81 volunteer post-menopausal women who have been taking hormone replacement treatment (HRT) were divided randomly into two groups: exercise group (which wasomposed of sub-maximal aerobic exercises for a 6-week period 3 times a week) and control group (received no training intervention). At the end of 6 weeks exercise period, they found statistically significant differences in quality of life, strength, endurance, flexibility and balance parameters in the exercise group 24 . However, Kanemaru et al. randomly assigned sixty-three osteoporotic women over 60 years to 12 months of muscle exercise or to no intervention, they proved that QOL, grip strength and maximum walking speed increased significantly in the intervention group, while there were no improvements in any of the parameters in the control group 25  Although the exact mechanism for the effect of exercises on mental health is still unknown, several physiological and psychological mechanisms have been proposed, including increased feelings of self-efficacy, self-perceptions of control, reduced emotional strain and physiological responses to stress, and beneficial effects on neurotransmitters 32 . In addition, physical activity appears to stimulate neurogenesis 33 , enhance neuronal survival 34 and increase synaptic plasticity 35 . Exercise promotes brain vascularization 36,37 . Social contact may be an important mechanism, and subjects who take regular exercise may, as a result, get positive feedback from other people and an increased sense of self-worth 38 .
In our study, the mean values of TNF-α, IL-2, IL-4, IL-6 and CRP were significantly decreased in both groups. In addition, there was a significant difference between both groups at the end of the study with more reduction of group (A) received aerobic exercise training. This means that in obese post-menopausal women aerobic exercise is more appropriate for modulating inflammatory cytokine levels than is resisted exercise training. These results are in line with many previous studies 39 The exact mechanisms by which physical activity may reduce inflammation are not entirely understood, there are some data pointing to factors that may contribute to an effect of repeated bouts of muscle contraction leading to improvements in inflammatory status over time as exercise training-induced improvements in inflammatory status may also result from the modulation of intracellular signaling pathways and cellular function that are mediated by nitric oxide (NO) and ROS 51 . Moreover, the potential mechanisms for the anti-inflammatory effect of exercise may include reduced percentage of body fat and macrophage accumulation in adipose tissue, muscle-released IL-6 inhibition of TNF-α and the cholinergic anti-inflammatory pathway 52 .
The current study has important strengths and limitations. The major strength is the supervised nature of the study. However, all exercise sessions were supervised. Moreover, the study was randomized; hence, we can extrapolate adherence to the general population. In the other hand, the major limitations is only post-menopausal women enrolled in the study, so the value of this study only related to women in this age group, also small sample size in both groups may limit the possibility of generalization of the findings in the present study. Finally, within the limit of this study, aerobic exercise training is recommended for modulation of low grade systemic inflammation and quality of life among obese post-menopausal women. Further researches are needed to explore the impact of weight reduction on quality of life and other biochemical parameters among post-menopausal women.

Conclusion
The current study provides evidence that weight reduction program improves biochemical & clinical parameters and quality of life among obese post-menopausal women. The strengths of this trial include its large sample size and randomized controlled design. There is no doubt that further studies are necessary to understand cellular and molecular mechanisms involved in relationships among weight reduction and changes of overall subscales of SF-36.
under grant no. (G-4-142-1439). The authors, therefore, acknowledge with thanks DSR for technical and financial support.