Interestingly, reduced levels of orexin are seen in patients with OSA,95 and orexin knockout mice show exaggerated sleep apneas96 and an attenuated hypercapnic chemoreflex.97 It is also notable that orexin signaling is involved in the regulation of feeding and metabolism, and knockout mice have a tendency for obesity,98 a possible basis for mechanistic link between obesity and OSA.91 This evidence concerns the gene HCRT and obesity due to melanocortin 4 receptor deficiency.