Overexpression of the Mitochondrial T3 Receptor p43 Induces a Shift in Skeletal Muscle Fiber Types

被引:45
作者
Casas, Francois [1 ,2 ,3 ]
Pessemesse, Laurence [1 ,2 ,3 ]
Grandemange, Stephanie [1 ,2 ,3 ]
Seyer, Pascal [1 ,2 ,3 ]
Gueguen, Naig [1 ,2 ,3 ]
Baris, Olivier [1 ,2 ,3 ]
Lepourry, Laurence [1 ,2 ,3 ]
Cabello, Gerard [1 ,2 ,3 ]
Wrutniak-Cabello, Chantal [1 ,2 ,3 ]
机构
[1] INRA, Differenciat Cellulaire & Croissance UMR866, F-34060 Montpellier, France
[2] Univ Montpellier I, Montpellier, France
[3] Univ Montpellier 2, Montpellier, France
来源
PLOS ONE | 2008年 / 3卷 / 06期
关键词
D O I
10.1371/journal.pone.0002501
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In previous studies, we have characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor and consequently stimulating mitochondrial activity and mitochondrial biogenesis. We have established the involvement of this T3 pathway in the regulation of in vitro myoblast differentiation. We have generated mice overexpressing p43 under control of the human alpha-skeletal actin promoter. In agreement with the previous characterization of this promoter, northern-blot and western-blot experiments confirmed that after birth p43 was specifically overexpressed in skeletal muscle. As expected from in vitro studies, in 2-month old mice, p43 overexpression increased mitochondrial genes expression and mitochondrial biogenesis as attested by the increase of mitochondrial mass and mt-DNA copy number. In addition, transgenic mice had a body temperature 0.8 degrees C higher than control ones and displayed lower plasma triiodothyronine levels. Skeletal muscles of transgenic mice were redder than wild-type animals suggesting an increased oxidative metabolism. In line with this observation, in gastrocnemius, we recorded a strong increase in cytochrome oxidase activity and in mitochondrial respiration. Moreover, we observed that p43 drives the formation of oxidative fibers: in soleus muscle, where MyHC IIa fibers were partly replaced by type I fibers; in gastrocnemius muscle, we found an increase in MyHC IIa and IIx expression associated with a reduction in the number of glycolytic fibers type IIb. In addition, we found that PGC-1 alpha and PPARd, two major regulators of muscle phenotype were up regulated in p43 transgenic mice suggesting that these proteins could be downstream targets of mitochondrial activity. These data indicate that the direct mitochondrial T3 pathway is deeply involved in the acquisition of contractile and metabolic features of muscle fibers in particular by regulating PGC-1 alpha and PPAR delta.
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页数:10
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