Fatty acid binding protein genes are known to include the 1-kb sequence, upstream of the initiation codon, 3 indel polymorphisms and 4 single nucleotide polymorphisms (SNPs), and there are 9 different types of FABP genes depending on each tissue. Among them, FABP2 genes are 3.4 kb in size and are located in the region of chromosome 4q 28-31, and they consist of 4 exons (700 bp) separated by 3 introns (2,650 bp) [22]. As guanine at codon 54 of FABP2 gene transforms into adenine, the alanine-threonine substitution of amino acid is reported to be associated with insulin resistance [3]. FABP2 is a relatively small protein (15 kDa) which is abundantly distributed in small intestine’s epithelial cells, and is known as one of the genes that participate in the intracellular metabolism and the transport of fatty acids [14]. However, the exact functions of FABP2 have never been revealed clearly. Many studies have mainly focused on the roles of FABP2 as a transcytoplasmic fatty acid carrier and a transmitochondrial fatty acid carrier as well as on its function of relieving intracellular enzymes’ hypofunction caused by long chain fatty acids. And it has been reported that FABP2 also serves as a free radical scavenger or removes peroxidized acids from cells [15].

Especially, as the affinity of those FABP2 which contain threonine at Codon 54 of the gene to long chain fatty acids is nearly twice greater than those including alanine [3], it can increase the absorption of fat, and an increased in serum free fatty acids (FFA) can cause insulin resistance by accelerating the intracellular oxidization of fat acids. As a matter of a fact, some studies targeting Japanese, Pima Indian and Caucasian people reported that the Ala54Thr polymorphism of FABP2 gene is associated with insulin resistance [23]. Other studies, which used Koreans as their subject groups to assess the correlation between the polymorphs of FABP2 genes and internal energy metabolism, said that in comparison with the control group, the experimental group containing Thr54 allele did not show any significant differences in terms of BMI, blood lipid and blood sugar levels on an empty stomach, but their basal insulin concentration increased and their insulin resistance indicator based on the Homeostatic Model Assessment (HOMA) also went up [1,13]. In addition, although the basal metabolism rate between the polymorphs of the two base sequences showed no significant differences, the fat oxidization rate of the Thr54 allelomorphic character was observed to be higher than that of the Ala54 allelomorphic character, which indicated that the FABP2 gene polymorphism could cause insulin resistance in Koreans by bringing about a change to fat metabolism [1]. Many previous studies have already found out a possibility of FABP2 as a candidate gene associated with obesity and insulin resistance. It reported that dietary treatments and exercise programs designed to control the FABP2 genes could reduce obesity levels, blood lipid concentrations, blood pressure and insulin resistance by a significant degree, and the variation in control capacity reflected the differences in gene polymorphs [1,2,6].

As diseases with genetic predisposition such as insulin resistance and non insulin-dependent diabetes are increasing at a fast clip at home and abroad due to an increase in obese population, studies have been actively conducted to find out the genetic causes to prevent and cure those diseases and to develop various medical treatments. About 40-70% of obesity and various chronic diseases including all types of Hypokinetic diseases are ascribed to genetic factors [3]. A more systematic experiment verification process needs to be conducted based on scientific logics for studies on the causes of these diseases, prevention by exercise, treatment efficacy, etc. To make this happen, it is the prerequisite to find out those candidate genes associated with obesity and chronic diseases and identity the exercise benefits of these genes. However, those studies which used Korean as a subject group have reported so far that these possible candidate genes had a very limited influence on the exercise benefits. Therefore, this study aims to find out the impact of the Ala54Thr polymorphism of FABP2 on obesity and biochemical indicators through a 12 week-long aerobic exercise training by targeting Korean middle-aged women with abdominal obesity as its subject group.

The 12 weeks of aerobic exercise training, considering the FABP2 Ala54Thr genetic polymorphism, improved the obesity indices such as weight, %bf, BMI, waist measurement, WHR, visceral fat area (VFA), and subcutaneous fat area, and enhanced the heart rate and cardiorespiratory fitness when resting. It also improved fasting insulin concentration, Oral Glucose Tolerance Test (OGTT) AUC index regardless of the genetic modification of the FABP2 Ala54Thr gene. In a mutant type, which the FABP2 Ala54Thr gene was mutated, the total area of the abdomen, systolic blood pressure, diastolic blood pressure, total cholesterol, LPL, LDL, and HOMA index were significantly improved and in the wild type, which the gene was not mutated, HDLC, FFA, blood glucose, and the blood glucose level of 120 minutes of OGTT were significantly improved. In other words, the 12 weeks of aerobic exercise training considering the FABP2 Ala54Thr genetic polymorphism, enhanced the obesity indices and biochemical indices of middle-aged Korean women with abdominal obesity in both wild type and mutant type, and the genetic sensitivity toward the enhancement was low.

The currently reported physiological roles of the body of FABP2 are as follows: restraining fatty acid from being combined with cell solute, cell membrane, or various cell components; delivering the fatty acid in cytoplasm to small cell organisms as a fatty acid deliverer. [19]. When the fatty acid does not melt into the aqueous solution, FABP2 minimizes the thermodynamic energy requirements for the fatty acid to melt into the aqueous solution easily, and when the lipid affects the gene expression through peroxisome proliferator-activated receptor (PRAP), FABP2 is able to deliver the regulatory lipid to the cell nucleus [22]. As the results of tracking observation for the study of the FABP2 Ala54Thr gene, obesity, blood lipids, insulin resistance, and the type 2 diabetes, the mutant type of this gene is related to obesity, hyperlipidemia, insulin resistance, and type 2 diabetes depending on age, disease, and lifestyle in specific races such as Pima Indian, Mexican American, Caucasian, Japanese, and Korean. In other words, the FABP2 Ala54Thr gene mutation increases the risk factors related to obesity and insulin resistance when resting, but the improvement effect when participating in an exercise program along with a dietary control such as low-calorie diets, and low fat diets is rather high. However, the researches which have conducted until now to prove the exercise effects according to the gene mutation are insufficient. [1,2,6,7,9,10,11,17,23]. Takakura, who reported the obesity index changes as participating in the FABP2 Ala54Thr intervention program, showed that as the results of participating in 6 months of dietary restriction (1,200kcal/day) and walking 10,000 steps a day, the visceral white adipose tissues reduction was low in the T allelomorphic character. But this study showed that the abdominal visceral fat and subcutaneous fat were improved as the results of 12 weeks aerobic exercise training regardless of the gene mutation. In this study, only participants lifestyles such the physical activities and dietary intake were investigated, and diet was not controlled, but the results are similar to those of exercising between 3 months and 6 months with dietary control. More interesting results are that this program brought not only the obesity indices reduction but also the cardiorespiratory fitness increase along with positive symptoms on blood indices. In the Luis study (2006), as the results of aerobic exercise, which took 60 minutes a day and more than 3 times a week along with low calorie diet (1,520 kcal; 52% carbohydrate, 25% fat, 23% protein), FABP2 improved significantly the obesity indices and the cardiorespiratory fitness, and the study also showed that there are differences in obesity indices improvement of the Ala54 allele, and in the systolic blood pressure and the glucose improvement of the Thr54 allele depending on the gene mutation occurrence. Similarly, this study showed the improvement of blood pressure in mutant type. [6-8,10] Furthermore, there was improvement in TC, LPL, LDLC, HOMA index, insulin, OGTT AUC in mutant type, and there was improvement in NEFA, glucose, OGTT 120 minutes glucose in wild type. Like these, the blood lipids and insulin resistance index were improved regardless of the gene mutation.

This study did not monitor the lifestyles of all participants, but at least the participants in this study showed the improvement in obesity indices, blood pressure, blood lipids, and insulin resistance according to the aerobic exercise training regardless of the FABP2 Ala54Thr gene mutation when considering the results presented in <Table 2>, which shows that there is not statistical difference in average intake calories a day and physical activities between FABP2 Ala54Thr polymorphism of 1.43 million people who participated in the program from the 3rd round. But the researches, which have been conducted until now, for the FABP2 Ala54Thr gene and lifestyle change, are very limited and the results cannot present a matched genetic effect. Even though this study is not sufficient to prove the genetic effects targeting middle-aged Korean women with abdominal obesity, this study showed low genetic sensitivity of the Ala54Thr mutation of the FABP2 gene compared to other characteristics in the improvement effect as the response to the exercise training stimulation in a large-scale intervention exercise with monitoring of the lifestyles (daily physical activity and dietary intake) of some participants.

The results of studies about relations of FABP2 Ala54Thr gene mutation with obesity, blood lipids, insulin resistance, and the type 2 diabetes, which have been conducted until now, differ depending on the race, and only two studies have been reported in Korea, therefore additional researches may be required. Most of advanced researches in and out of Korea are epidemiological studies, which were conducted once and focus on dependent variable relations in dietary control, complex program with dietary control and exercise. This study can be regarded as meaningful as a research which proves the genetic sensitivity effect on exercise through the FABP2 Ala54Thr gene through a large-scale aerobic exercise training targeting middle-aged Korean women with abdominal obesity.

As the test results to find if the FABP2 Ala54Thr gene of middle-aged Korean women with abdominal obesity affects the improvement of obesity indices, blood lipids, blood glucose variables, and insulin resistance indices if participating in the 12 weeks of aerobic exercise training, the following conclusion was obtained.

As a summary of the conclusions above, the 12 weeks of aerobic exercise targeting middle-aged Korean women with abdominal obesity according to the FABP2 Ala54Thr gene polymorphism, improves obesity indices, cardiorespiratory fitness, blood lipids, and blood glucose and insulin resistance index regardless of the gene mutation.