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Orexin system is expressed in avian muscle cells and regulates mitochondrial dynamics

Significance statement 

With world population predicted to increase to between 9 and 10 billion by 2050, demand for meat and egg protein will concomitantly increase. Meeting this demand poses a significant challenge, particularly when coupled with the additional metabolic stressors associated with rising temperatures due to climate change. Broiler chickens play a key role in worldwide meat production and understanding the basic molecular mechanisms underlying their growth performance are of uppermost interests for improving feed efficiency and poultry production. Our work represents the first evidence of the orexin system in the skeletal muscle of avian species and identifies orexin playing a key role in mitochondrial dynamics. Chickens are characteristically hyperglycemic and insulin resistant, and animal production efficiency is tied directly to energy use and over 90% of the ATP produced is by mitochondria. Mitochondria dysfunction is associated with many pathophysiological processes including insulin resistance and type 2 diabetes mellitus (T2DM). Our findings open new vista on the role of orexin as a molecular signature in muscle energy metabolism that may have potential implications not only in avian biology for health and feed efficiency improvement, but also in molecular medicine for therapeutic perspectives.

Figure Legend.

Immunofluorescence staining showed that orexin and its related receptors are expressed in muscle QM7 (a), recombinant orexin B (100 nM) alters mitochondrial dynamics (fusion/fission)-related protein expression determined by Western blot (b), and affects mitochondrial biogenesis (c and d).

Orexin system expressed in avian muscle cells regulates mitochondrial dynamics . Global Medical Discovery












Journal Reference

Lassiter K1, Greene E1, Piekarski A1, Faulkner OB1, Hargis BM1, Bottje W1, Dridi S2. Am J Physiol Regul Integr Comp Physiol. 2015 ;308(3):R173-87.

1Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, Arkansas.

2Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, Arkansas [email protected]


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.

Copyright © 2015 the American Physiological Society.

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