Obesity is a global problem that is associated with high mortality and morbidity. Several studies has shown that obesity increases the risk of cardiovascular disease, renal impairment, diabetes, and even certain cancers ^{1– 3} . Meanwhile, the World Health Organization (WHO) showed that in the last 4 decades obesity rates have increased 10 times worldwide ³ . This phenomenon is worrisome because there is an increasing number of people who have a high risk of developing various diseases associated with obesity.

Some studies show that there is a strong association between the incidence of obesity with the level of physical activity and high fat diet intake. Individuals with low physical activity levels are known to have a higher risk of developing obesity ^{4, 5} . Physical activity is also known to have a role on lowering blood glucose levels, improving homeostasis in people with diabetes mellitus, decreasing production of oxidative stress, lowering triglyceride levels in the body, increasing endogenous antioxidants, and can also maintain telomere length, thus reducing cardiovascular metabolic disease risk ^{6– 8} .

The role of physical activity in decreasing the risk of cardiovascular metabolic mortality and morbidity is thought to be mediated by maintaining the length of telomeres ⁹ . A study performed by Goglin et al. demonstrates the association between telomere shortening and increased 5-year mortality in patients with acute coronary syndromes. This study also showed that a decrease in telomere shortening rate would be followed by a decrease in mortality rate ¹⁰ .

The rate of shortening of the telomere can be suppressed through a healthy lifestyle such as healthy diet and physical activity ^{9, 11} . Certain types of food have been shown to have a correlation with telomere length. A Mediterranean-rich diet of olive oil (38% of total energy as fat) has been observed to maintain telomere length ¹² . In contrast, a high western type diet of sugar and red meat is associated with shortening of the telomere ¹² .

The aim of this study was to explore the effect of aerobic physical exercise on telomere length under high fat-diet conditions to provide information for further research.

The characteristics of the animals are shown in Table 1. All the animals were in good condition throughout the length of study. There was no significant difference in age, body weight, Lee index and telomere length between control and treatment groups.

There was an increase in relative telomere length at weeks 4 and 8 compared to week 0 in both groups. At week 4, the relative telomere length of the control group (2.231) did not differ much with the treatment group (1.802) when compared to week 0 of control group. At week 8, there was a progressive increase of relative telomere length in both groups compared to week 0 and week 4. Relative telomere length increase in week 8 of the control group was much higher (178.62) compared to week 8 treatment group (74.86) ( Figure 1; Table 2).

One important structures located at the ends of the linear chromosomes is the telomere. In human cells, they are composed of TTAGGG repeats and a number of proteins. Their function is to protect the integrity and stability of the DNA ¹⁴ .

Many studies showed that telomere length is influenced by a number of factors ^{9, 12, 15} . Sedentary lifestyle, high blood glucose levels, and increased percentage of body fat have a negative influence on telomere length. The underlying mechanism have been suggested as being mediated through oxidative stress and inflammation ¹⁶ .

Exercise as a lifestyle intervention has been associated with longer leukocytes telomere length ¹⁵ . A study by Cherkas on 2401 subject showed that telomere length has a direct relation with increased level of physical activity ¹⁷ . An observation of physical activity and telomere length by Du et al. on 7813 adult women concluded that moderate and vigorous intensity activity increased telomere length compared with least active women ¹⁸ . Ludlow et al. studied the effect of physical activity on telomere length in three different groups: sedentary, moderate and overtraining. The result showed a positive effect on telomere length in the moderate group ¹⁹ .

To date, to our knowledge, very few studies have investigated the relative effect of a specific diet on telomere length. Cassidy et al. found that total fat intake was only inversely associated with leukocytes telomere length and higher polyunsaturated fatty acids (PUFA) intake, specifically linoleic acid intake, was inversely associated with leukocytes telomere length ¹¹ . Li et al. found that there was no difference in telomere length between consumption of fish oil-rich diet and soy oil-rich diet ²⁰ . Kiecolt-Glaser et al. compared telomere length between subjects with n-6 PUFA and n-3 PUFA supplementation. They found that telomere length is longer in subject with omega 3 or n-3 PUFA supplementation (high in fish oil) compared to n-6 PUFA supplementation ²¹ .

Results from our current study showed a lengthening of relative telomere length in both groups in week 4 and week 8. This was in contrast with studies showing telomeres usually shortened with age ⁹ ., but there are also studies which indicate that in vivo, telomere may shorten or elongate, and leukocyte telomere length may fluctuates within months ^{22, 23} .

In general, preserved telomere length and lengthening of telomere are considered as something good because it is thought to play an important role in extending the biological age of cells ^{12, 21, 24} .

Nevertheless, studies have also shown that telomere lengthening can be an initial response that arises after exposure to low doses of various carcinogenic chemicals in vitro and in experimental animals ²³ . Zhang et al. concluded from their study that subject with longer telomere length had a higher risk of getting lung cancer, and this was especially true for men ²⁵ .

The positive associations between high fat-diet conditions and telomere length is difficult to explain because a high fat-diet is associated with increased risk of various diseases. Telomeres generally shorten with age, thus, the discovery of telomer elongation in the provision of high-fat diet can be regarded as something that deviates from normal condition. Therefore, the positive associations between high fat-diet conditions and telomere length observed in this study are notable.

Telomere will shorten at each cell division. Telomeres that elongate excessively in both groups in this study may indicate a prolonged period before apoptosis, and this could indicates a change from normal cell function. Currently, the implications of excessive telomere lengthening are still unknown. Our result shows that aerobic exercise can act as a barrier to progressive changes that occur in the relative telomere length caused by a high-fat diet condition. Modulation of oxidative stress in the body is one possible mechanism that may explain how aerobic exercise resist relative telomere changes. Aerobic exercise upregulate genes that encode various antioxidant enzymes. Several studies shows that regular physical exercise increase the body's endogenous antioxidant activity and thus increase body’s resistance to oxidation events ^{15, 26} .

Our study showed that exposure to a high fat-diet plays an important role to the emergence of altered telomere length, and aerobic exercise could reduce the progression of the alteration in length. Our results support the hypothesis that leukocyte telomere length is associated with daily dietary intake and physical activities. Further investigation is still needed to explore the mechanism and implications of telomere length changes found in this study.

The data referenced by this article are under copyright with the following copyright statement: Copyright: � 2018 Santoso DIS et al.

Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

Dataset 1: Raw data including the relative telomere length for control and treatment groups at week 0, 4 and 8, and 2 ^-ΔΔ ^Ct calculations. DOI, 10.5256/f1000research.15127.d211681 ²⁷ .