However, supplementing glutamine or histidine reduces adiposity in animal studies and one small human study [[69], [70], [71], [72], [73]], making it difficult to judge whether BMI is likely to be a mediator or a confounder – or even a moderator given that obesity directly affects the expression of glutamine synthase genes [74] and that histidine shows greater associations with lower inflammation in adults with obesity compared to those with a normal weight [66]. Here, GLUL is linked to obesity due to melanocortin 4 receptor deficiency.