Authors: Han, Bing; Zhu, Mei J.; Ma, Changwei; Du, Min

Source: Applied Physiology, Nutrition, and Metabolism, Volume 32, Number 6, December 2007 , pp. 1115-1123(9)

Publisher: NRC Research Press

Abstract:

Inactivity is known to induce muscle atrophy, which is associated with insulin and insulin-like growth factor-1 (IGF-1) resistance, but the associated mechanisms remain poorly defined. The hindlimb unloading model has been used to reduce muscle activity. The objective of this study was to show the effect of hindlimb unloading on IGF-1 signaling and AMP-activated protein kinase (AMPK) activity in rat soleus and extensor digitorum longus (EDL) muscles. Twelve 7-week-old male Sprague-Dawley rats were assigned to 2 treatments: (i) rats without hindlimb unloading (Con) and (ii) rats with hindlimb unloading (Unload). After 2weeks of treatment, the soleus and EDL muscles were dissected and used for biochemical analyses. Hindlimb unloading induced severe muscle atrophy in soleus muscle (0.122± 0.007g for Con vs. 0.031± 0.004g for Unload, p<0.01), but only slight atrophy in EDL muscle. The phosphorylation of AMPK (p<0.05) and its downstream substrate, acetyl-CoA carboxylase (ACC) (p<0.01) were reduced in soleus muscle due to unloading. The concentration of insulin receptor substrate-1 (IRS-1) and phosphorylation of IRS-1 at Ser_636-639 and Ser₇₈₉ were also reduced. Downstream IGF-1 signaling was downregulated in Unload rats. A reduction in IGF-1 concentration in unloaded soleus muscle was also observed. A slight reduction in AMPK activity and IGF-1 signaling were observed in EDL muscle. Since AMPK controls the sensitivity of IGF-1 signaling through phosphorylation at Ser₇₈₉, the reduction in AMPK activity is expected to reduce the response of downstream IGF-1 signaling to IGF-1; this, in combination with reduced IGF-1 concentration, might be responsible for the severe muscle atrophy observed in unloaded soleus muscle.

L'inactivité physique cause, on le sait, l'atrophie des muscles; cette dernière est associée à la résistance de l'insuline et du facteur de croissance insulinomimétique de type 1 (IGF-1), mais les mécanismes sont mal compris. Nous avons utilisé le modèle de la patte arrière délestée de sa charge pour diminuer l'activité physique. Le but de l'étude est de d'analyser l'effet du délestage de la patte arrière sur la signalisation de l'IFG-1 et l'activité de l'AMP protéine kinase activée (AMPK) du soleus et de l'extensor digitorum longus (EDL) chez le rat. Douze rats Sprague-Dawley âgés de 7 semaines sont répartis dans deux groupes, l'un sans délestage (Con) et l'autre, avec délestage (Unload). Après deux semaines d'expérimentation, les deux muscles sont disséqués et préparés à des fins d'analyse biochimique. Le délestage de la patte arrière cause une importante atrophie du soleus (Con, 0,122± 0,007g comparativement à Unload, 0,031± 0,004g, p< 0,01), mais seulement une atrophie mineure de l'EDL. À cause du délestage, on observe dans le soleus une diminution de la phosphorylation de l'AMPK (p< 0,05) et de son produit en aval, l'acétyl coenzyme A carboxylase (ACC) (p< 0,01). On observe aussi une diminution de la concentration des substrats des récepteurs à l'insuline (IRS-1) en Ser_636-639 et en Ser₇₈₉. De plus, on observe chez les rats délestés une régulation à la baisse des substances en aval de l'IGF-1. Finalement, on observe aussi une diminution de la concentration de IFG-1 dans le soleus délesté et une diminution de l'activité de l'AMPK et de la signalisation de l'IGF-1 dans le muscle EDL. Comme l'AMPK contrôle la sensibilité des signaux issus de l'IFG-1 par la phosphorylation en Ser₇₈₉, la diminution de l'activité de l'AMPK devrait limiter la signalisation en aval de IFG-1 à IFG-1; l'atrophie importante observée dans le soleus délesté serait probablement due à la diminution de la concentration de IFG-1.

Document Type: Research article

Publication date: 2007-12-01

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• This bimonthly journal has a 30-year history of publishing, first as the Canadian Journal of Sport Sciences, and later as the Canadian Journal of Applied Physiology. It publishes original research articles, reviews, and commentaries, focussing on the application of physiology, nutrition, and metabolism to the study of human health, physical activity, and fitness. The published research, reviews, and symposia will be of interest to exercise physiologists, physical fitness and exercise rehabilitation specialists, public health and health care professionals, as well as basic and applied physiologists, nutritionists, and biochemists.
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