1. Introduction
Obesity is as one of the major pathological conditions and one of the most important factors in development of metabolic syndrome, type 2 diabetes and cardiovascular diseases [3] . Obesity is linked to these diseases via creation and development of chronic inflammation [25]. Insulin resistance, as an important feature of obesity, and associated risk factors induce several pre-inflammatory factors including interleukin-6, tumor necrosis factor (TNF)-α and growth/differentiation factor-15 (GDF-15) through disruption in pancreatic beta cells [25]. The GDF-15 is a member of the growth factor-β family that can be activated as a metabolic regulator from various tissues including macrophages, liver, and white adipose tissue [23].
As an adipokin like adiponectin and leptin, it can regulate glucose and fat metabolism as well as the type of stress-sensitive cytokine that regulates energy homeostasis [23]. Physical activity is the component of obesity treatment and prevention of many chronic diseases that can be applied in various ways [11]. Pre-inflammatory and inflammatory cytokines secreted from different tissues in response to exercise, have been implicated as potential molecular mechanisms of adaptation to exercise [9]; however, it is not well known whether these adaptation created by exercise can affect the GDF-15 level as an anti-obesity potential [15]. Therefore, this study aimed to evaluate the response of glucose, insulin and GDF-15 levels to two types of intermittent and continues exercises among inactive obese men. 
2. Materials and Methods
The study population consisted of 60 inactive male students with obesity at Guilan University who were studying in the academic year 2017-18. Of these, 8 students (Mean±SD age, 25.75±37.2 years; body mass index, 31.96±3.03 Kg/m2) were selected as study samples and were asked to perform two types of high-intensity (HIIT) intermittent activity and medium-intensity (MIT) continues activity using crossover and randomized crossover designs and then attend a control session with no activity. At the first session, anthropometric characteristics (height, weight, body fat percentage and body mass index), and physiological parameters such as maximal oxygen uptake (VO2max) (by Bruce Test) were measured. After one week, subjects were randomly assigned to crossover exercise protocols for three weeks.
The HIIT intermittent activity consisted of 10-min warm up at an intensity of 50- 60% VO2max, six 1-min interval activity at intensity of 85% VO2max and 4-min active recovery at an intensity of 50-60% VO2 max and finally, 5-min cooling down, while the MIT continues activity included 30-min running on the treadmill at an intensity of 65% VO2max. Subjects did not perform any activity in control session. Blood samples were collected from the subjects three times before, immediately and 24 hours after the recovery.
3. Results
The anthropometric and physiological responses to the exercise conditions are presented in Table 1.

The results of data analysis using repeated measures ANOVA showed that the serum GDF-15 levels were significantly increased after HIIT and MIT exercises (P=0.001); however, there was no significant difference between the two exercises protocol in increasing serum levels of GDF-15 immediately after exercise (P˃0.33). Furthermore, there was no significant difference in serum insulin levels between two exercises (P˃0.13); however, there was a significant difference in serum glucose level such that both types of HIIT and MIT protocols significantly reduced serum glucose level at 3 time intervals (before, after and 24 hours after exercise) compared to the control group (P˃0.005), but no difference was found between the two exercise protocols (P˃0.48).
4. Conclusion
The present study investigated the acute effect of two types of HIIT intermittent and MIT continues exercises on serum levels of GDF-15, insulin and glucose in inactive obese men. The result showed that serum levels of GDF-15 immediately was increased significantly after both types of exercises, but decreased significantly during the 24-hour recovery period after both protocols. This result is in agreement with the result of Kleinert  et al. [15]. They also reported a significant increase in the GDF-15 level of healthy subjects following a MIT continuous activity at intensity of 67% VO2max. Elevated serum levels of GDF-15 were also observed within one hour of exercise. In this regard, it can be stated that GDF-15 may increase in response to stress and cellular damage caused by acute exercise, which may continue for several hours after exercise [12].
The decrease of GDF-15 level until a level lower than the baseline level during the recovery period after exercise may indicate potential anti-inflammatory effects of exercise by reducing the level of anti-inflammatory cytokines in later hours. Tchou et al. also reported a decrease in GDF-15 level 48 hours after a session of intense endurance exercise in elite soccer players [14]. GDF-15 is an indicator of the extent of damage to the cardiovascular system and its function. Tchou et al. showed that GDF-15 reflects a transient endothelial dysfunction in athletes who participated in a heavy, long-range exercise activity. In animal models, GDF-15 serum from the heart in response to ischemia/reperfusion injury, compressive overload, and heart failure is released by pre-inflammatory cytokines such as interleukin-6 and oxidative stress-dependent pathway [14].
Galliera et al reported the GDF-15 serum as a parameter monitoring cardiovascular function after a session of intense activity in elite rugby players [12]. GDF-15 can exert its anti-obesity and anti-diabetic effect by regulating mitochondrial biogenesis-dependent pathways. This metabolic effect of GDF-15 may be a possible reason for the improvement of glucose metabolism in the present study. It seems that the increase in GDF-15 level induced by acute exercise activity may be an effective factor in improving plasma glucose in obese men. Our study showed that exercise can increase plasma GDF-15 level and improve glucose metabolism in sedentary obese males.
Ethical Considerations
Compliance with ethical guidelines
The present study was approved by the Research Ethics Committee of Guilan University of Medical Sciences (Code: IR.GUMS.REC.1397.017).
Funding
The present paper was extracted from the MSc. thesis of the first author, Department of Exercise Physiology, Faculty of Physical Education Sciences, and Guilan University.
Authors' contributions
Writing: Bahman Mirzaei; Sources and validation: Hadi Golpasandi and Shadi Golpasandi; Methodology and data analysis: Hadi Golpasandi; Project editing and management: Bahman Mirzaei.
Conflicts of interest
The authors declared no conflict of interest.
 

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