This study showed that habitual dietary intakes of TFA and PUFA were positively associated with apelin gene expression in visceral and subcutaneous adipose tissues among obese participants. Findings revealed that dietary intake of n-3 fatty acids was positively associated with apelin mRNA expression in visceral and subcutaneous among non-obese and obese participants.
It should be noted that the present study was the first investigation that assessed the relationship between habitual intake of fatty acids and apelin mRNA expression. Previous data on the relationship between TFA and apelin gene expression in adipose tissue was limited to findings in rats(13, 20); generally, apelin expression in adipose tissue and apelin concentrations increased in the rodents on a high-fat diet, compared with those on a standard diet (20) (13). Although animal studies show that apelin mRNA levels in adipose tissue and serum concentrations after a high-fat diet increased simultaneously (14, 21); another study demonstrated that despite the increase in apelin gene expression in adipose tissue in response to the high-fat diet, apelin concentration did not change significantly (15). Moreover, despite human studies investigating the impact of a low-calorie diet on apelin concentration among obese patients, no information regarding dietary components was reported (22–24); hence, we were unable to determine the relation of dietary components, especially dietary intakes of fatty acids on apelin. In the current study, we observed that TFA was associated with apelin gene expression in the obese subjects after controlling for BMI, thus, suggesting that the amount of body fat was not a mediator for an increase in apelin gene expression.
Although we found no significant difference between apelin gene expression among the obese and non-obese individuals, a higher concentration of apelin in patients with obesity was previously reported (22, 23, 25, 26). Regarding apelin gene expression and secretion, no direct association between gene expression pattern and secretion of apelin was found (27). Moreover, Celik et al. reported that by a 1.12% reduction (28) and Heinonen et al. by a 14.28% reduction BMI (24), no significant change in apelin concentrations was observed. Therefore, in addition to weight status, some other related factors might also modify the concentration of apelin. Insulin level is a potential factor in apelin changes. Decreased insulin concentration has possibly more influence than merely weight loss. Therefore, insulin levels may have a mediated role in the existing direct relationship between apelin and excess weight (13, 14, 20, 27, 29). Participants who were free of diabetes and hypertension were recruited for the present study. Furthermore, the nutrient content of the habitual diet may be among other factors that influence apelin.
High intakes of PUFA and n-3 fatty acids predicted apelin gene expression in both subcutaneous and visceral adipose tissue in all the weight groups. Apelin expression in response to EPA intervention was investigated in adipose tissue (13, 14); EPA supplementation (1 g/kg) in rats with a high-fat diet increased apelin gene expression (14). Moreover, in mice that received a high-fat diet enriched with 36 g/kg EPA, adipose tissue apelin gene expression was increased (13). Furthermore, intervention by EPA in a high-fat diet among mice led to a reduced level of insulin and glucose as well as improved insulin sensitivity through the increment of β oxidation in insulin-dependent organs and enhanced the expression of apelin and apelin receptor (13, 30); similarly, apelin was also demonstrated to enhance glucose tolerance in mice with obesity and insulin resistance (31). In addition, the present study showed n-3 fatty acids predicted apelin gene expression of a similar amount in both adipose tissues in obese subjects and 1-SD increase in n-3 fatty acids had association with approximately 0.6 unit increases in both visceral and subcutaneous apelin mRNA levels. In addition, it seems that n-3 fatty acid intakes increased apelin gene expression more in subcutaneous adipose tissue among obese subjects than in non-obese ones (0.7 vs. 0.5). Perez-Echarri et al. showed that in rats, overfeeding with a diet rich in SFA increased apelin gene expression in visceral fat (14). However, apelin gene expression in rats fed with a high-SFA diet along with EPA treatment was higher than that fed to rats i.e., high-fat diet (14).
The potential mechanism of the effect of dietary fatty acids intake on apelin is not well understood; however, some mediator pathways can be suggested. Insulin, leptin, and peroxisome proliferator-activated receptor-γ (PPARγ) are potential candidates for the regulation of the diet-induced apelin levels. (8, 13, 32–35).
There were limitations that should be stated. Small sample sizes limited our power to detect statistical associations. Despite the relatively large magnitude of the β standard in the dietary exposure and apelin mRNA levels, the exploratory insight of the current study should be considered. Therefore, our results need to be confirmed in the cohort and trial studies. Because the design of the current study was a cross-sectional, causal relationship cannot be inferred. However, since there is less probable that apelin induce dietary fat quality, we assumed that our conclusion to be likely that dietary fat may have an impact on apelin gene expression. Moreover, the lack of measuring apelin protein concentration and APJ gene expression was another limitation.