title: High level of uncoupling protein 1 expression in muscle of transgenic mice selectively affects muscles at rest and decreases their IIb fiber content.
abstract: 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.
authors.affiliation: Ceremod CNRS UPR9078, 9 rue Jules Hetzel, 92190 Meudon, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Couplan
authors.forename: Chantal
authors.initials: C
authors.lastname: Gelly
authors.forename: Marc
authors.initials: M
authors.lastname: Goubern
authors.forename: Christophe
authors.initials: C
authors.lastname: Fleury
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesson
authors.forename: Mathieu
authors.initials: M
authors.lastname: Silberberg
authors.forename: Eric
authors.initials: E
authors.lastname: Thiaudiere
authors.forename: Philippe
authors.initials: P
authors.lastname: Mateo
authors.forename: Michel
authors.initials: M
authors.lastname: Lonchampt
authors.forename: Nigel
authors.initials: N
authors.lastname: Levens
authors.forename: Catherine
authors.initials: C
authors.lastname: De Montrion
authors.forename: Silvia
authors.initials: S
authors.lastname: Ortmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Klaus
authors.forename: Maria-Del-Mar
authors.initials: MD
authors.lastname: Gonzalez-Barroso
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cassard-Doulcier
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricquier
authors.forename: A Xavier
authors.initials: AX
authors.lastname: Bigard
authors.forename: Philippe
authors.initials: P
authors.lastname: Diolez
authors.forename: Frederic
authors.initials: F
authors.lastname: Bouillaud
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002149:Energy Intake; D004734:Energy Metabolism; D006321:Heart / Q000502:physiology; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism; D024101:Mitochondrial Proteins; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009200:Myocardial Contraction; D009928:Organ Specificity; D010641:Phenotype; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D012044:Regression Analysis; D012146:Rest; D000071256:Uncoupling Protein 1
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D010725:Phosphocreatine; D000255:Adenosine Triphosphate