The current study showed that adherence to a low-energy, moderate fiber diet significantly increases serum BDNF levels. However, serum BDNF levels did not show any significant difference between the TT / TC and CC genotypes. These results were consistent with similar studies conducted on overweight and obese individuals. For example, Aryana et al. reported that a reduction of 7 kg over a three-month period, in 70 obese adults with insulin resistance, lead to a significant increase in serum BDNF. In Aryana et al, the distribution of macronutrients in the diet was similar to the present study, and was reported as 55% carbohydrate, 20% protein and 25% fat [22]. In addition, in another study by Kuo et al. (37), serum BDNF levels reportedly increased significantly over the course of a three month, which only included recommendations for modification lifestyle included increased consumption of vegetables and reduced consumption of simple sugars and saturated fats, albeit in a population of patients with Schizophrenia [23]. Moreover, comparable results, to the present study, were also observed in a study by Lee et al., whom implemented a diet of 1,200 kilocalories, lifestyle changes and increased physical activity [31]. However, whilst the positive effects of dietary restriction or adaptation have been well reported, the responses have been notably different, depending upon the population of inquiry. Lee et al reported that, in 36 obese patients with metabolic syndrome and 25 healthy individuals, serum BDNF levels were higher in obese subjects than in normal subjects. It has been asserted that increasing serum BDNF levels after glucose intake was associated with obesity, in the same way as with weight loss, serum BDNF levels decreased with glucose consumption compared with baseline values [24]. In fact, the increase in BDNF levels after glucose consumption is associated with body weight [32]. However, serum BDNF concentrations were not significantly related to body fat mass in some studies [20, 33].
Such contradictory results were also found in another study on children, in which, after one year of lifestyle changes in individuals, the serum BDNF concentration in obese children was higher than normal weight counterparts. Problematically, it was not specified what type of lifestyle changes had a greater effect on its increase [25].
The difference between the results of the studies mentioned above and the present study may be due to differences in the type of intervention, age of subjects, differences in lifestyle characteristics, BMI of the participants, different methods of serum BDNF detection, and adjustment for different confounding factors. The present study showed that there was no significant difference in serum level of BDNF in TT / TC and CC genotypes. Several studies have suggested that one of the APOA-II polymorphisms known as T < C-265 polymorphism is associated with an increase in inflammation in various diseases [34]. In addition, a recent study by Moradi et al. found that gene expression and serum levels of VCAM1 in the CC group had a significant reduction following a low-energy diet [35]. On the other hand, it has been shown that inflammation is one of the most important reasons for lowering the serum levels of BDNF, which has been well documented in diabetics and heart patients due to elevated inflammatory factors such as VCAM-1. As in the study by Lee et al., where high levels of VCAM-1 were significantly associated with low serum BDNF levels in cardiac patients [36]. Therefore, it appears that an energy-restricted dietary intervention in diabetic and obese patients with APOA-II T < C-265 polymorphisms may be effective, justifiable and tolerable. However, our results did not support this hypothesis, and conceivably because the present study allocated participants to two genotypic groups, this limited the number of participants, thereby confounding our ability to discern significant differences between the TT / TC and CC genotypic groups.
In general, BDNF and its receptor TrkB are widely expressed in the brain of growing and mature mammals. Intracellular signaling stimulated by BDNF / TrkB is essential for neuronal survival, cellular differentiation, cell migration, synaptic synthesis and synaptic flexibility or 'plasticity’ [16, 17, 37]. Minor changes in BDNF levels or repeated expression of uncertain single nucleotide polymorphism(SNPs) in the BDNF gene are related to behavioral changes including abnormal nutritional behaviors, episodic memory changes (events), and sensitivity to psychiatric disorders of anxiety and depression in humans and animal models [38, 39]. In recent years, numerous studies have been conducted on the association of BDNF and various mental illnesses such as stress and anxiety [40], autism [41], bipolar disorder [42, 43], depression [44, 45], and eating disorders [46, 47]. Furthermore, it has been shown that serum levels of BDNF are associated with levels of nutrient peptides such as leptin and cholecystokinin (CCK) [48, 49]. Although there is tentative evidence for the mechanistic action of BDNF, it is far from elucidatory or confirmatory, and, as such, it is strongly recommended that the relationship between BDNF levels and hormones involved in appetite and fat mass, and mechanism of action be further investigated.