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莱克多巴胺诱导猪骨骼肌中的基因差异表达。

Ractopamine induces differential gene expression in porcine skeletal muscles.

作者信息

Gunawan A M, Richert B T, Schinckel A P, Grant A L, Gerrard D E

机构信息

Department of Animal Sciences, Purdue University, West Lafayette 47907, USA.

出版信息

J Anim Sci. 2007 Sep;85(9):2115-24. doi: 10.2527/jas.2006-540. Epub 2007 Apr 27.

DOI:10.2527/jas.2006-540
PMID:17468428
Abstract

Ractopamine (RAC) improves growth by increasing lean accretion and decreasing fat deposition through repartitioning nutrients from adipose tissue to skeletal muscle. Although the process is not completely understood, RAC alters the proportion of muscle fiber type composition toward a faster-contracting phenotype. Because one of the primary determinants of contractile speed is the relative abundance of myosin heavy chain (MyHC) isoforms and because the genes encoding these isoforms are transcriptionally regulated, RAC likely alters MyHC gene expression. Using real-time PCR, the relative abundance of transcripts of individual type I, IIA, IIX, and IIB, and total MyHC, as well as glycogen synthase, citrate synthase, lactate dehydrogenase, peroxisome proliferator activated receptor alpha, beta1-adrenergic receptor (AR), and beta2-AR were determined in the LM of 44 pigs fed RAC (20 mg/kg) for 0, 1, 2, or 4 wk. In addition, MyHC isoform expression was determined in the LM and red semitendinosus and white semitendinosus muscles of 48 pigs fed RAC (20 mg/kg) for shorter periods of 12, 24, 48, or 96 h. Type I MyHC expression was unaffected (P > 0.73) by RAC administration. Type IIA MyHC expression decreased (P < 0.0001) by 96 h, was lower (P < 0.0001) by 1 wk, and returned to normal by 4 wk. Type IIX MyHC mRNA decreased (P < 0.001) by 2 wk and continued to decrease (P < 0.0001) by 4 wk. Most interesting was an increase (P < 0.0001) in type IIB MyHC by 12 h, which was maintained at an elevated level throughout the 4-wk feeding period. Abundance of glycogen synthase transcript was increased (P < 0.05) by 12 h, but was not different from controls at 2 wk, and was lower (P < 0.01) at 4 wk. Gene expression of beta1-AR was not affected by feeding RAC, whereas beta2-AR gene expression was decreased (P < 0.05) by 2 wk. These data show MyHC genes are differentially regulated by RAC and suggest that the beta adrenergic agonist-induced repartitioning effect is, in part, mediated by changing muscle fiber type-specific gene expression, perhaps through the beta2-AR.

摘要

莱克多巴胺(RAC)通过增加瘦肉沉积和减少脂肪沉积来改善生长,其机制是将营养物质从脂肪组织重新分配到骨骼肌。尽管这一过程尚未完全明确,但RAC会使肌纤维类型组成比例朝着收缩更快的表型转变。由于收缩速度的主要决定因素之一是肌球蛋白重链(MyHC)亚型的相对丰度,且编码这些亚型的基因受转录调控,所以RAC可能会改变MyHC基因的表达。运用实时定量PCR技术,测定了44头饲喂RAC(20毫克/千克)0、1、2或4周的猪的腰大肌中I型、IIA型、IIX型和IIB型MyHC以及总MyHC的转录本相对丰度,同时还测定了糖原合酶、柠檬酸合酶、乳酸脱氢酶、过氧化物酶体增殖物激活受体α、β1-肾上腺素能受体(AR)和β2-AR的转录本相对丰度。此外,还测定了48头短期(12、24、48或96小时)饲喂RAC(20毫克/千克)的猪的腰大肌、红色半腱肌和白色半腱肌中MyHC亚型的表达。I型MyHC的表达不受RAC给药影响(P>0.73)。IIA型MyHC的表达在96小时时下降(P<0.0001),1周时更低(P<0.0001),4周时恢复正常。IIX型MyHC的mRNA在2周时下降(P<0.001),4周时继续下降(P<0.0001)。最有意思的是,IIB型MyHC在12小时时增加(P<0.0001),并在整个4周的饲喂期内维持在较高水平。糖原合酶转录本的丰度在12小时时增加(P<0.05),但2周时与对照组无差异,4周时更低(P<0.01)。饲喂RAC对β1-AR的基因表达无影响,而β2-AR的基因表达在2周时下降(P<0.05)。这些数据表明MyHC基因受RAC的差异调控,提示β-肾上腺素能激动剂诱导的重新分配效应部分是通过改变肌纤维类型特异性基因表达介导的,可能是通过β2-AR实现的。

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