Orexin A and B, orexigenic peptides produced primarily by the lateral 
hypothalamus that signal through two G protein-coupled receptors, orexin 
receptors 1/2, have been implicated in the regulation of several physiological 
processes in mammals. In avian (nonmammalian vertebrates) species; however, the 
physiological roles of orexin are not well defined. Here, we provide novel 
evidence that not only is orexin and its related receptors 1/2 (ORXR1/2) 
expressed in chicken muscle tissue and quail muscle (QM7) cell line, orexin 
appears to be a secretory protein in QM7 cells. In vitro administration of 
recombinant orexin A and B (rORX-A and B) differentially regulated prepro-orexin 
expression in a dose-dependent manner with up-regulation for rORX-A (P < 0.05) 
and downregulation for rORX-B (P < 0.05) in QM7 cells. While both peptides 
upregulated ORXR1 expression, only a high dose of rORX-B decreased the 
expression of ORXR2 (P < 0.05). The presence of orexin and its related receptors 
and the regulation of its own system in avian muscle cells indicate that orexin 
may have autocrine, paracrine, and/or endocrine roles. rORXs differentially 
regulated mitochondrial dynamics network. While rORX-A significantly induced the 
expression of mitochondrial fission-related genes (DNM1, MTFP1, MTFR1), rORX-B 
increased the expression of mitofusin 2, OPA1, and OMA1 genes that are involved 
in mitochondrial fusion. Concomitant with these changes, rORXs differentially 
regulated the expression of several mitochondrial metabolic genes (av-UCP, 
av-ANT, Ski, and NRF-1) and their related transcriptional regulators (PPARγ, 
PPARα, PGC-1α, PGC-1β, and FoxO-1) without affecting ATP synthesis. Taken 
together, our data represent the first evidence of the presence and secretion of 
orexin system in the muscle of nonmammalian species and its role in 
mitochondrial fusion and fission, probably through mitochondrial-related genes 
and their related transcription factors.