Regulation of muscle fiber type and running endurance by PPARdelta.
Regulation of muscle fiber type and running endurance by PPARdelta.
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DOI：
10.1371/journal.pbio.0020294
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发表时间：
2004-10
期刊：
影响因子：
9.8
通讯作者：
Evans RM
中科院分区：
文献类型：
--
作者：
Wang YX;Zhang CL;Yu RT;Cho HK;Nelson MC;Bayuga-Ocampo CR;Ham J;Kang H;Evans RM
耐力运动训练可以通过触发基因表达的脚本变化来促进适应性肌纤维转化和线粒体生物发生的增加。然而，目前还没有发现能够指导这一过程的转录因子。我们描述了一种能够连续奔跑的老鼠的工程，这种老鼠的距离是野生型同伴的两倍。这是通过在骨骼肌中靶向表达活化形式的过氧化物酶体增殖物激活受体δ (PPARδ)来实现的，该受体δ诱导形成I型肌纤维数量增加的开关。用PPARδ激动剂治疗野生型小鼠，在肌肉中引起类似的I型纤维基因表达谱。此外，即使在不运动的情况下，这些基因产生的纤维也能通过改善代谢谱来抵抗肥胖。这些结果表明，复杂的生理特性，如疲劳、耐力和跑步能力，可以通过分子分析和操纵。骨骼肌中过氧化物酶体增殖物激活受体δ的工程化表达增加了I型肌肉纤维，使改良小鼠的奔跑距离是野生型小鼠的两倍
Endurance exercise training can promote an adaptive muscle fiber transformation and an increase of mitochondrial biogenesis by triggering scripted changes in gene expression. However, no transcription factor has yet been identified that can direct this process. We describe the engineering of a mouse capable of continuous running of up to twice the distance of a wild-type littermate. This was achieved by targeted expression of an activated form of peroxisome proliferator-activated receptor δ (PPARδ) in skeletal muscle, which induces a switch to form increased numbers of type I muscle fibers. Treatment of wild-type mice with PPARδ agonist elicits a similar type I fiber gene expression profile in muscle. Moreover, these genetically generated fibers confer resistance to obesity with improved metabolic profiles, even in the absence of exercise. These results demonstrate that complex physiologic properties such as fatigue, endurance, and running capacity can be molecularly analyzed and manipulated. Engineered expression of the peroxisome proliferator-activated receptor δ in skeletal muscle increases type I muscle fibers allowing the modified mice to run twice the distance of wild-type littermates
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DOI：
10.1073/pnas.012610299
发表时间：
2002-01-08
影响因子：
11.1
作者：
Barak, Y;Liao, D;Evans, RM
通讯作者：
Evans, RM
影响因子：
15.9
作者：
LILLIOJA, S;YOUNG, AA;BOGARDUS, C
通讯作者：
BOGARDUS, C
影响因子：
4.8
作者：
Luquet, S;Lopez-Soriano, J;Grimaldi, PA
通讯作者：
Grimaldi, PA
影响因子：
--
作者：
Dressel, U;Allen, TL;Muscat, GEO
通讯作者：
Muscat, GEO
影响因子：
4.8
作者：
Ryder, JW;Bassel-Duby, R;Zierath, JR
通讯作者：
Zierath, JR