Data from several independent in vitro and rodent models support the hypothesis that OXA mediated increase of energy consumption suggests orexin’s obesity resistance may be partially dependent on signaling cascades involving MAPK, PGC-1α, and HIF-1α, regulation of these pathways ultimately induces increased SPA and obesity resistance (78). This evidence concerns the gene HCRT and obesity due to melanocortin 4 receptor deficiency.