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

被引:47
作者
Lassiter, Kentu [1 ]
Greene, Elizabeth [1 ]
Piekarski, Alissa [1 ]
Faulkner, Olivia B. [1 ]
Hargis, Billy M. [1 ]
Bottje, Walter [1 ]
Dridi, Sami [1 ]
机构
[1] Univ Arkansas, Ctr Excellence Poultry Sci, Fayetteville, AR 72701 USA
关键词
orexin system; muscle; mitochondrial dynamics; fusion; fission; cellular bioenergetics; gene expression; SKELETAL-MUSCLE; PERIPHERAL-TISSUES; UNCOUPLING PROTEIN; INTRACEREBROVENTRICULAR INJECTION; CHICKEN HYPOTHALAMUS; PROTON CONDUCTANCE; INSULIN-RESISTANCE; COLD-ACCLIMATION; FEEDING-BEHAVIOR; NEONATAL CHICKS;
D O I
10.1152/ajpregu.00394.2014
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 down-regulation 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 (PPAR gamma, PPAR alpha, PGC-1 alpha, PGC-1 beta, 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.
引用
收藏
页码:R173 / R187
页数:15
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