To our knowledge, this cross-sectional study is the first study to have investigated the interaction between CAV-1 genotypes and dietary fat quality indices on VAI and BAI among overweight and obese women. Accordingly, our results showed that there may be an interaction between CAV-1 genotypes and dietary fat quality indices (CSI, W6/W3 ratio) on BAI and VAI in overweight and obese women.
We found that the interaction of increased adherence to W6/W3 ratio consumption with AA carriers of CAV-1 was positive on VAI and BAI, additionally, we noted a positive interaction between CSI with AA risk allele on VAI. To our knowledge, no study has been conducted directly on this subject, but according to some related studies, CAV-1 may have a direct impact on the regulation of HDL, TG, and cholesterol, and in general, CAV-1 impacts on fatty acid metabolism (21, 32, 33). In another study, the CAV-1 expression was decreased in adipocytes of obese subjects (34). An animal study showed that consumption of a high-cholesterol diet can affect the expression of CAV-1 (22). We found that the AA risk allele group of CAV-1 has higher BAI than other groups, whilst in terms of VAI, the AG genotype group was higher than others. BAI and VAI represent novel indicators of obesity that have been scarcely studied (35, 36). Female AA allele risk had a significantly higher BMI compared to the reference group (GG), which is consistent with previous studies (29). According to Catalan et al, CAV-1 expression in visceral adipose tissue and subcutaneous adipose tissue is associated positively BMI and body fat (32).
According to our results, females with the AG risk allele have higher WHR and DBP values in comparison to the GG group, whilst the value of HDL and LDL was higher in the reference group (GG). As previously mentioned, CAV-1 has a critical role in lipid homeostasis, which can affect adipose tissue, blood vessels, and liver, to alter the regulation of TG, cholesterol, VLDL, and HDL (33). However, our results did not show any significant difference in macronutrients, energy, and fat components of foods of subjects, with the only difference found in biotin and total fiber.
Caveolae are formed from lipid rafts and contain cholesterol, glycosphingolipids, and CAV-1 (37), and can elicit an uptake of lipid metabolites, including several fatty acid species, triacylglycerol, and cholesterol, (38–40). The roles of CAV-1 are variegated, with its’ most important functions in cholesterol homeostasis, signal transduction, cellular and systemic lipid metabolism, and regulation of lipid and lipoprotein metabolism (32, 33, 41). CAV-1 expressed in different parts of the body, such as fibroblasts, epithelial, and endothelial cells, and also in adipocytes (42). It is interesting that the CAV-1 works as an element in lipid droplets and can effect lipid droplet accumulation and breakdown (43). According to Chang et al, a high-fat diet causes CAV-1 to be secreted more in adipose tissue in comparison to a normal diet in mice, therefore, adipose tissue may be considered the main source of CAV-1 secretion (44). Razani et al found that CAV-1 in adipocyte and endothelial cells has an effect on obesity, mediated by diet (45). Moreover, some studies have shown that CAV-1 acts as a tumor suppressing protein by inhibiting the functional signaling activity of several mutated genes, and thus disrupts the cell transformation process (46–54). The mechanism by which CAV-1 acts as a tumor suppressor remains under investigation, however, may putatively be because CAV-1 is a scaffolding protein and interacts with and regulates signaling pathways, in addition to a possibility that this protein may regulate proto-oncogenes (12). Moreover, cytokines like TNF-A and IL-1B can effect CAV-1 mRNA expression (55).
CAV-1 is involved in lipogenesis and adipogenic processes as CAV-1 mRNA (56)., and CAV-1 can functionally suppress transforming growth factor-beta (TGF-β) by modifying the phosphorylation state of SMAD., Another potential mechanism is that the interaction between CAV-1 with transforming growth factor-beta type 1 receptor (TαR-1) may influence TGF-β inhibition (55). Further, CAV-1 can impact cytokine signaling by interactions with the janus kinase (JAK) family, cytokine receptors, and the proteasome pathway (15, 57).
There are several limitations in the present study that must considered when interpreting out findings. This study was a cross-sectional study, thereby precluding causal inferences being drawn. Next, the sample size used to conduct this study was small, and we used a FFQ to investigate the intakes of subjects, which, given its’ self-reported nature, may be influenced by recall bias. Furthermore, this study was conducted only on women, so that results may not generalized to all sexes. Nevertheless, despite the noted limitations, our study has numerous strengths, including; this is, to our knowledge, the first study to have investigated the interaction between CAV-1 genotypes with dietary fat quality indices on VAI and BAI among overweight and obese women, moreover, we used detailed genetic factors in the study. Further, since we conducted this study on women only, greater specificity and insight maybe gleaned.