Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.

The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers a...

Full description

Bibliographic Details
Main Authors: Carlos R Bueno Júnior, Lucas C Pantaleão, Vanessa A Voltarelli, Luiz Henrique M Bozi, Patricia Chakur Brum, Mayana Zatz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3448675?pdf=render
_version_ 1818939939491938304
author Carlos R Bueno Júnior
Lucas C Pantaleão
Vanessa A Voltarelli
Luiz Henrique M Bozi
Patricia Chakur Brum
Mayana Zatz
author_facet Carlos R Bueno Júnior
Lucas C Pantaleão
Vanessa A Voltarelli
Luiz Henrique M Bozi
Patricia Chakur Brum
Mayana Zatz
author_sort Carlos R Bueno Júnior
collection DOAJ
description The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM [AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPARδ agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Treatments started when the animals were two months old and were maintained for one month. A significant functional improvement (p<0.05) was observed in animals submitted to the combination of ET and EM. CK levels were decreased and the expression of proteins related to oxidative metabolism was increased in this group. There were no differences among the groups in the intracellular calcium handling protein expression. To our knowledge, this is the first study that tested the association of ET with EM in an experimental model of muscular dystrophy. Our results suggest that the association of ET and EM should be further tested as a potential therapeutic approach in muscular dystrophies.
first_indexed 2024-12-20T06:31:43Z
format Article
id doaj.art-6e0c0508862742d09e63883eba553e3e
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-20T06:31:43Z
publishDate 2012-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-6e0c0508862742d09e63883eba553e3e2022-12-21T19:50:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4569910.1371/journal.pone.0045699Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.Carlos R Bueno JúniorLucas C PantaleãoVanessa A VoltarelliLuiz Henrique M BoziPatricia Chakur BrumMayana ZatzThe present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM [AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPARδ agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Treatments started when the animals were two months old and were maintained for one month. A significant functional improvement (p<0.05) was observed in animals submitted to the combination of ET and EM. CK levels were decreased and the expression of proteins related to oxidative metabolism was increased in this group. There were no differences among the groups in the intracellular calcium handling protein expression. To our knowledge, this is the first study that tested the association of ET with EM in an experimental model of muscular dystrophy. Our results suggest that the association of ET and EM should be further tested as a potential therapeutic approach in muscular dystrophies.http://europepmc.org/articles/PMC3448675?pdf=render
spellingShingle Carlos R Bueno Júnior
Lucas C Pantaleão
Vanessa A Voltarelli
Luiz Henrique M Bozi
Patricia Chakur Brum
Mayana Zatz
Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.
PLoS ONE
title Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.
title_full Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.
title_fullStr Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.
title_full_unstemmed Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.
title_short Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.
title_sort combined effect of ampk ppar agonists and exercise training in mdx mice functional performance
url http://europepmc.org/articles/PMC3448675?pdf=render
work_keys_str_mv AT carlosrbuenojunior combinedeffectofampkpparagonistsandexercisetraininginmdxmicefunctionalperformance
AT lucascpantaleao combinedeffectofampkpparagonistsandexercisetraininginmdxmicefunctionalperformance
AT vanessaavoltarelli combinedeffectofampkpparagonistsandexercisetraininginmdxmicefunctionalperformance
AT luizhenriquembozi combinedeffectofampkpparagonistsandexercisetraininginmdxmicefunctionalperformance
AT patriciachakurbrum combinedeffectofampkpparagonistsandexercisetraininginmdxmicefunctionalperformance
AT mayanazatz combinedeffectofampkpparagonistsandexercisetraininginmdxmicefunctionalperformance