ABSTRACT
BACKGROUND: The regulation of mitochondrial energy metabolism by adenylate activated protein kinase (AMPK) is an important cause of fat accumulation in obese and type 2 diabetic patients. Chronic inflammation will further induce skeletal muscle atrophy. Aerobic exercise can increase the activity of AMPK and regulate energy metabolism, but the mechanism of aerobic exercise in improving skeletal muscle atrophy in type 2 diabetes by increasing AMPK is unclear. OBJECTIVE: To explore the effect of aerobic exercise on skeletal muscle atrophy in type 2 diabetic rats and the role of AMPK. METHODS: The model of type 2 diabetic rats was established by high fat feeding and streptozotocin injection, and the rats were divided into four groups: control group (n=6), exercise group (n=9), diabetic control group (n=8) and diabetic exercise group (n=12). The control group and the diabetic control group were kept for 4 weeks, and the exercise group and the diabetic exercise group were given aerobic exercise intervention for 4 weeks. After 4 weeks of aerobic exercise (running speed 16 m/min, 60 min/d, 5 days/week), the muscle atrophy of soleus was observed by immunohistochemical staining. The expression levels of AMPK, PGC-1 α, MAFbx and MuRF1 were detected by western blot assay. The study protocol was approved by the Ethical Committee of School of Sport Science, Beijing Sport University in China on June 25, 2016, with approval No. 2016014. RESULTS AND CONCLUSION: Blood glucose of type 2 diabetes rats was significantly increased, and body weight and insulin levels of type 2 diabetes rats were significantly decreased (P < 0.01). The mean cross sectional area of soleus fiber in the diabetic group was significantly lower than that in the control group (P < 0.01), and the cross sectional area of soleus muscle fiber in the diabetic exercise group was significantly higher than that in the diabetic group (P < 0.01). The expression levels of AMPK and PGC-1 α in the soleus muscle of diabetic rats were significantly lower than those in the control group, and the expression levels of MAFbx and MuRF1 were significantly higher than those in the control group (P < 0.01). The expression levels of AMPK, MAFbx and MuRF1 in the diabetic exercise group were significantly higher than those in the diabetic group (P < 0.01). These results suggest that aerobic exercise can improve mitochondrial function, inhibit the expression of MAFbx and MuRF1, improve skeletal muscle atrophy and restore the metabolic balance of type 2 diabetes mellitus to some extent by activating AMPK/PGC-1α signaling pathway.
ABSTRACT
The expression of MuRF1 and MAFbx in a denervated muscle has previously been studied. However, the expression of MuRF1 and MAFbx in the recipient and donor muscles after muscle transfer for reconstruction of joint function has not been sufficiently investigated. Forty-two adult Sprague-Dawley rats were divided into 7 groups: normal, 1 w post-, 2 w post-, and 4 w post-musculocutaneous nerve transection; and 1 w post-, 2 w post-, and 4 w post-reconstruction of elbow flexion. Muscle wet weights were assessed, and MuRF1 and MAFbx mRNA expressions were detected by polymerase chain reaction. The length of the oblique part of the pectoralis major of an SD rat is sufficient for suture to the insertion of the biceps brachii tendon. The muscle wet weight and the wet weight retention rate of the biceps brachii continued to decline after musculocutaneous nerve transection and a gradual increase was noted after the oblique part of the pectoralis major was transferred for reconstruction of elbow flexion. The oblique part of the pectoralis major showed a decrease of only 26%. The upregulated expression of MuRF1 and MAFbx in the biceps brachii reached a peak 2 w after denervation and 1 w after elbow flexion reconstruction, with an increase of 15% and 4%, respectively. This was followed by downregulation; however, the expression had not normalized at postoperative 4 w. The increased expression of MuRF1 (17%) and MAFbx (1%) in the oblique part of the pectoralis major at postoperative 1 w had decreased to below normal levels at postoperative 4 w. The transfer of the oblique part of the pectoralis major for elbow flexion reconstruction after musculocutaneous nerve transection can downregulate the expression of MuRF1 and MAFbx in the recipient muscle and causes only transient damage to the donor muscle in rats.
La expresión de MuRF1 y MAFbx en un músculo denervado ha sido estudiada previamente. Sin embargo, la expresión de MuRF1 y MAFbx en los músculos receptores y donantes después de la transferencia del músculo para la reconstrucción de la función articular no se ha investigado lo suficiente. Cuarenta y dos ratas adultas Sprague-Dawley fueron divididas en 7 grupos: normales, 1 semana post-, 2 semanas post- y 4 semanas post-transección del nervio musculocutáneo; y 1 semana post-, 2 semanas post-, y 4 semanas post-reconstrucción de la flexión del codo. Se evaluó el peso de los músculos húmedos, y las expresiones de MuRF1 y MAFbx mRNA fueron detectadas a través de reacción en cadena de la polimerasa. La longitud de la parte oblicua del músculo pectoral mayor de una rata Sprague-Dawley es suficiente para realizar la sutura en la inserción del tendón de músculo bíceps braquial. El peso húmedo del músculo bíceps braquial y su tasa de retención siguieron disminuyendo después de la sección del nervio musculocutáneo y un aumento gradual se observó después de la transferencia de la parte oblicua del músculo pectoral mayor para la reconstrucción de la flexión del codo. La parte oblicua del músculo pectoral mayor mostró una disminución de sólo 2-6%. La expresión regulada por incremento de MuRF1 y MAFbx en el bíceps braquial alcanzó un peak 2 semanas después de la denervación y 1 semana después de la reconstrucción de la flexión del codo, con un incremento del 15% y el 4%, respectivamente. Esto fue seguido por un regulación en baja. Sin embargo, la expresión no se normalizó en el postoperatorio de las 4 semanas. El aumento de la expresión de MuRF1 (17%) y MAFbx (1%) en la parte oblicua del músculo pectoral fue mayor en el postoperatorio de 1 semana, mientras que se encontró por debajo de los niveles normales en el postoperatorio de 4 semanas. La transferencia de la parte oblicua del músculo pectoral mayor para la reconstrucción de la flexión del codo después de la sección del nervio musculocutáneo puede regular a la baja la expresión de MuRF1 y MAFbx en el músculo receptor y provocar solo un daño transitorio en el músculo donado en ratas.
Subject(s)
Animals , Rats , Muscle Proteins/metabolism , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/metabolism , Musculocutaneous Nerve/surgery , Nerve Transfer/methods , Muscle, Skeletal/surgery , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
[Objective]This study was designed to investigate the effects of 5-aminoimidasole-4-carboxamide ribonucleoside (AICAR)on activity of transcription factor Forkhead O 3a(FOXO3a)and expression of ubiquitin ligase muscle atrophy F-box (MAFbx),and to explore the role of adenosine monophosphate-activated protein kinase(AMPK)on proteolysis pathways in eardiomyocytes.[Methods]The effect of AICAR on activation of AMPK was observed.Cultured neonatal rat cardiomyocytes was treated with AICAR in different concentration.Cultured cardiomyocytes were then divided into three groups:control group,AICAR group,AICAR+Compound C group.Effects of AMPK activation on phosphorylation of FOXO3a and expression of MAFbx in cardiomyocytes were detected using Western blot.[Results]①Compared with control group,activity of AMPK in cultured cardiomyocytes was increased after treatment with 0.25 mmol/L or 0.5 mmol/L AICAR for 6 h(P＜0.05),and the activity of AMPK was further enhanced after treatment with 1.0 mmol/L or 2.0 mmol/L AICAR for 6 h(P＜0.01).②Activation of AMPK by AICAR significantly increased the transcriptional activity of FOXO3a(P＜0.01),and enhanced MAFbx protein expression in cardiomyocytes when comparing with control group(P＜0.01),however,specific AMPK antagonist Compound C markedly reversed these effects induced by AICAR.[Conclusion]AMPK may regulate cardiomyocytes proteolysis by activation of FOXO3a transcription factor,and up-regulation of MAFbx protein expression.