Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function
Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function
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DOI：
10.1152/ajpcell.00030.2008
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发表时间：
2008-07-01
影响因子：
5.5
通讯作者：
Hawke, Thomas J.
中科院分区：
文献类型：
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作者：
Krause, Matthew P.;Liu, Ying;Hawke, Thomas J.
脂联素（Adiponectin，Ad）与多种疾病状态相关，并介导抗糖尿病和抗炎作用。虽然它最初被认为是有限的，广告的表达脂肪细胞，我们在这里证明，广告在小鼠骨骼肌和分化的L 6肌管内表达，通过RT-PCR，Western印迹和免疫组化分析评估。连续肌肉切片染色的纤维类型，脂质含量，和广告显示，肌细胞内广告表达升高的肌纤维始终IIA和IID型纤维与可检测到较高的肌细胞内脂质（IMCL）含量。为了确定Ad对肌肉表型和功能的影响，我们使用了Ad-null [敲除（KO）]小鼠模型。24周龄KO小鼠的体重显著增加[相对于野生型小鼠（WT）+5.5 +/- 3%]，未观察到肌肉质量变化。IMCL含量显著增加（+ 75.1 +/- 25%），而KO小鼠的附睾脂肪量虽然升高，但与WT相比没有差异（+ 35.1 +/- 23%; P = 0.16）。纤维类型组成没有改变，尽管KO小鼠的IIB型纤维面积增加（+ 25.5 +/- 6%）。原位肌肉刺激显示KO小鼠的峰值强直力相对于WT较低（+ 47.5 +/- 6%），低频疲劳率无变化。这些数据表明，Ad表达的缺乏导致骨骼肌收缩功能障碍和表型变化。此外，我们证明，广告在骨骼肌中表达，其肌内定位与升高IMCL，特别是在IIA/D型纤维。
Adiponectin (Ad) is linked to various disease states and mediates antidiabetic and anti-inflammatory effects. While it was originally thought that Ad expression was limited to adipocytes, we demonstrate here that Ad is expressed in mouse skeletal muscles and within differentiated L6 myotubes, as assessed by RT-PCR, Western blot, and immunohistochemical analyses. Serial muscle sections stained for fiber type, lipid content, and Ad revealed that muscle fibers with elevated intramyocellular Ad expression were consistently type IIA and IID fibers with detectably higher intramyocellular lipid (IMCL) content. To determine the effect of Ad on muscle phenotype and function, we used an Ad-null [knockout (KO)] mouse model. Body mass increased significantly in 24-wk-old KO mice [+5.5 +/- 3% relative to wild-type mice (WT)], with no change in muscle mass observed. IMCL content was significantly increased (+ 75.1 +/- 25%), whereas epididymal fat mass, although elevated, was not different in the KO mice compared with WT (+ 35.1 +/- 23%; P = 0.16). Fiber-type composition was unaltered, although type IIB fiber area was increased in KO mice (+ 25.5 +/- 6%). In situ muscle stimulation revealed lower peak tetanic forces in KO mice relative to WT (+ 47.5 +/- 6%), with no change in low-frequency fatigue rates. These data demonstrate that the absence of Ad expression causes contractile dysfunction and phenotypical changes in skeletal muscle. Furthermore, we demonstrate that Ad is expressed in skeletal muscle and that its intramyocellular localization is associated with elevated IMCL, particularly in type IIA/D fibers.