High level of uncoupling protein 1 expression in muscle of transgenic mice selectively affects muscles at rest and decreases their IIb fiber content

被引:56
作者
Couplan, E
Gelly, C
Goubern, M
Fleury, C
Quesson, B
Silberberg, M
Thiaudière, E
Mateo, P
Lonchampt, M
Levens, N
de Montrion, C
Ortmann, S
Klaus, S
Gonzalez-Barroso, MDM
Cassard-Doulcier, AM
Ricquier, D
Bigard, AX
Diolez, P
Bouillaud, F
机构
[1] CNRS, UPR 9078, F-92190 Meudon, France
[2] INRA, Lab Nutr & Securite Alimentaire, F-78352 Jouy En Josas, France
[3] Univ Victor Segalen, CNRS, UMR 5536, F-33076 Bordeaux, France
[4] Ctr Rech, Serv Sante Armees, Unite Bioenerget & Environm, F-38702 La Tronche, France
[5] Univ Paris Sud, Fac Pharm, INSERM, U446, F-92296 Chatenay Malabry, France
[6] Inst Rech Servier, F-92150 Suresnes, France
[7] German Inst Human Nutr, DIfE, D-14558 Bergholz Rehbrucke, Germany
关键词
D O I
10.1074/jbc.M206726200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed in skeletal muscle and heart of transgenic mice at levels comparable with the amount found in brown adipose tissue mitochondria. These transgenic mice have a lower body weight, and when related to body weight, food intake and energy expenditure are increased. A specific reduction of muscle mass was observed but varied according to the contractile activity of muscles. Heart and soleus muscle are unaffected, indicating that muscles undergoing regular contractions, and therefore with a continuous mitochondrial ATP production, are protected. In contrast, the gastrocnemius and plantaris muscles showed a severely reduced mass and a fast to slow shift in fiber types promoting mainly IIa and IIx: fibers at the expense of fastest and glycolytic type IIb fibers. These observations are interpreted as a consequence of the strong potential dependence of the UCP1 protonophoric activity, which ensures a negligible proton leak at the membrane potential observed when mitochondrial ATP production is intense. Therefore UCP1 is not deleterious for an intense mitochondrial ATP production and this explains the tolerance of the heart to a high expression level of UCP1. In muscles at rest, where ATP production is low, the rise in membrane potential enhances UCP1 activity. The proton return through UCP1 mimics the effect of a sustained ATP production, permanently lowering mitochondrial membrane potential. This very likely constitutes the origin of the signal leading to the transition in fiber types at rest.
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页码:43079 / 43088
页数:10
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