In this study, we reported the novel finding that AA carriers of rs3807992 CAV1 gene variant had higher weight rather than other groups. In this manner, we should note that CAV1 is a main fatty acid-binding protein in adipocytes [20, 21]. CAV1 also directly binds to cholesterol. A high amount of cholesterol is one of the hallmarks of the biogenesis of specialized membrane lipid rafts, called caveolae. . Because of this, a defect in the CAV1 function would cause defects in lipid homeostasis and weight gain differences.
Currently, there are limited data considering the CAV1 gene and metabolic diseases, including obesity, metabolic syndrome, and diabetes. [23, 24].
Recent studies exhibited that CAV1 can be transmitted to lipid droplets. Therefore, it seems that the activity of CAV1is essential to preserve the perilipin function and the following lipid droplet integrity, and thus its absence can result in the alterations of lipid droplet size [25, 26]. In this context, the association between CAV1 variant and weight may also be due to the proposed functions of CAV1 in adipocytes, including, maintaining the integrity of the lipid droplet and transporting cholesterol and fatty acids. This study also showed that their animal model exhibited a larger white adipose tissue after a high-fat diet .
The abnormal function of CAV1 is highly connected to dyslipidemia since CAV1 has different metabolic functions, including regulating cholesterol transfer mechanisms and oxidized LDL receptors . However, the mechanisms that underlie the linkage between CAV1 gene polymorphisms and dyslipidemia have yet to be investigated. Previously, variants in the CAV1 gene have been connected to lip dystrophy, a disorder of unusual lipid distribution . Today, various genome-wide studies have supported the correlation between the CAV1 variants and dyslipidemia, for instance, the low HDL and high triglycerides [30, 31].
Previous studies also showed the role of CAV1 in cardio metabolic disorders. They investigated CAV1-deficient mice and observed dyslipidemia, insulin resistance, and hypertension. These results were also reported in human studies with CAV1 mutations who exhibit dyslipidemia, insulin resistance, and diabetes [23, 32, 33]. It is demonstrated that another variant of the CAV1 gene means rs926198 is linked to dyslipidemia, particularly low HDL cholesterol and also other metabolic disorders, including diabetes, insulin resistance, metabolic syndrome, and cardiovascular risk in Caucasians and Hispanics. Therefore, it may be considered as a marker for cardio metabolic risk factors in non-obese people .
Remarkably, both knockout and autosomal recessive mutations in the CAV1 gene correlate with alterations in lipid and glucose metabolism despite a lean phenotype with reduced adiposity [35, 36].
Here we also elucidated that there was no significant association between all of the nutrients intakes across the three alleles of CAV-1rs3807992 genotypes. More importantly, there was a significant interaction between MIND diet and genotype for dyslipidemia and the AA carriers with higher adherence to the MIND diet may exhibit lower dyslipidemia. Nevertheless, there was no remarkable interaction between MIND diet and genotype on dyslipidemia after adjustments.
Diets that particularly restrict calorie intake improve lipid profiles . Interestingly, it is declared that CAV1 variants correlate with lower expression of CAV1 and that CAV1 deficiency can affect different lipid and glucose mechanisms . We should note that there is no study considering certain diets in lean humans with CAV1 risk alleles. But, a recent study showed that a caloric restriction regimen greatly decreased bodyweight, triglyceride, cholesterol, and insulin resistance in CAV1 knockout mice . Another study showed that a high-fat diet-induced metabolic changes and CAV1 expression in subcutaneous adipocytes of rats .
Hypertension is regarded to follow a heritable pattern in family studies [41, 42]. Particularly, there is a certain region in chromosome 7 close to the CAV1 gene which is the most related region to both glucose and lipid metabolism but not augmented adiposity in Asian people . Moreover, it is reported that this particular region close to the location of the CAV1 gene was associated with metabolic syndrome .
Previous studies on CAV1 deficient rodents showed higher blood pressure and vascular dysfunction [44, 45]. Herein, we also find a significant association between CAV1 genotypes with DBP, which remained significant after adjustment for age, BMI, physical activity, and total energy intake. Interestingly, AA carrier was associated with higher weight and lower DBP. However, another study on a Caucasian cohort with subsequent replication in a Hispanic cohort did not observe any relationship between the CAV1 variant and hypertension .