Our results show that ingestion of an urban diet induces a higher increase in the plasma concentration of leucine, isoleucine, valine, phenylalanine, tyrosine and proline than ingestion of a rural diet in Mexican women from a rural area. A strength of this study is the fact that the same individuals where tested with both diets which decrease the effect of individual variation. Interestingly, the variations of BCAA and tyrosine were not directly associated with changes in plasma glucose and total cholesterol after the consumption of both diets. However, we observed that the elevation of BCAA and tyrosine with the urban diet was parallel to changes in serum triglycerides. Nonetheless, subjects fed the urban diet tended to increase plasma glucose concentration in the last hour of the study compared with subjects fed the rural diet. It is important to point out that with our study we cannot rule out that, in addition to the change in amount and type of protein, the presence of other components of the diet such as the amount of carbohydrates, fat and dietary fiber could directly impact glucose levels, insulin signaling or insulin secretion; for example, the urban diet has a higher proportion of simple carbohydrates, which have a higher insulinemic and glycemic index that can per se contribute to the development of insulin resistance. Further studies are need to assess the short- and long-term effects of the consumption of this diets on serum insulin and GLP1 levels to closely associate the changes in BCAA with insulin secretion and signaling. In addition, it is necessary to understand whether genetic variability between rural and urban population in Mexico as well as environmental conditions and physical activity can modify the biological response to the type of diet consumed.
Although the amount of protein consumed in the urban diet is greater than in the rural diet, why only these amino acids are increased requires further investigation. We can enumerate four possible mechanisms: 1) the presence of other components of the diet such as the amount and type of fiber that could alter the digestibility of the protein; 2) the fact that the first step of branched chain amino acid catabolism is extrahepatic which could delay their clearance from plasma; 3) an animal or vegetable based diet alters the gut microbiome [12], and this could modify the bacterial synthesis of branched chain amino acids; and 4) the rate at which each amino acid is incorporated in protein synthesis, i.e.: leucine is incorporated to proteins at a higher rate than isoleucine and valine.
Furthermore, there is controversy about the health implications of branched chain amino acids. In one hand, leucine activates the mTOR-S6K pathway, which inhibits the insulin receptor substrate 1(IRS1), thus, the over stimulation of this pathway by a high intake of BCAA leads to insulin resistance [3]. On the other hand, there is also evidence that high leucine intake can improve insulin sensitivity (reviewed by [13]. Our results suggest that this potential controversy depends on several factors that could contribute to such differences: 1) the source, i.e. the type of protein, vs the supplementation with BCAA or leucine, or 2) the context, i.e. a rich source of protein administered alone [14] or together with fat or complex/simple carbohydrates. In addition, beyond this controversy, it is not clear whether changes in BCAA are cause or consequence of insulin resistance.
Finally, we also observed an increase in plasma aromatic amino acid concentrations phenylalanine and especially tyrosine. An increase in serum tyrosine levels is accompanied by a concomitant increase in brain tyrosine concentration and catecholamines such as Norepinephrine (NE) [15]. As NE modulates food intake, then it is possible that the increase in tyrosine levels could modify food intake behavior. Intriguingly, we also observed an increase in proline after ingestion of the urban diet, however the biological significance of this increase is unclear. Therefore, the greater increase in both BCAA and tyrosine concentrations, could explain in part why immigrants are more susceptible to changes in body fat distribution [16] and to develop diseases related to over-nutrition such as obesity and diabetes [17,18]. In addition to immigrants, changes in feeding behavior affect rural populations. Nowadays, the food system in an increasing proportion of rural areas across low- and middle-income countries has changed drastically with the enormous penetration of super- and mega- market companies that increase the access to energy dense food [19]. In Mexico, this is reflected in the greater increase in the prevalence of overweight and obesity in rural (3.9%) compared to urban (2.5%) women in the last 6 years [20].