LEP and obesity due to melanocortin 4 receptor deficiency: BMI may indeed represent a confounders influencing both metabolic dysregulations and symptoms expressing altered energy intake processes (e.g. increased weight and appetite), but also a consequence (collider) of metabolic alterations affecting both metabolite concentrations and behavioral symptoms (e.g. leptin signaling disruption driving hyperphagia and energy accumulation, ultimately leading to obesity [35]).