HCRT and obesity due to melanocortin 4 receptor deficiency: These non-glucose roles enhance the understanding of orexin’s integrative function, as arousal and circadian alignment (e.g., via suprachiasmatic nucleus [SCN] inputs) directly influence metabolic outcomes like glucose tolerance, while reward and emotional regulation may indirectly affect feeding behaviors, linking to obesity and diabetes risk (Harris et al., 2005; Tsuneki et al., 2016).