Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation

Dyslipidemia is commonly linked to skeletal muscle dysfunction, accumulation of intramyocellular lipids, and insulin resistance. However, our previous research indicated that dyslipidemia in apolipoprotein E and low-density lipoprotein receptor double knock-out mice (ApoE/LDLR -/-) leads to improvem...

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Autores principales: Marta Tomczyk, Alicja Braczko, Patrycja Jablonska, Adriana Mika, Kamil Przyborowski, Agata Jedrzejewska, Oliwia Krol, Filip Kus, Tomasz Sledzinski, Stefan Chlopicki, Ewa M. Slominska, Ryszard T. Smolenski
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:0b28bbcba6ba443abf9519a38c17710c2021-11-25T17:54:46ZEnhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation10.3390/ijms2222122511422-00671661-6596https://doaj.org/article/0b28bbcba6ba443abf9519a38c17710c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12251https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Dyslipidemia is commonly linked to skeletal muscle dysfunction, accumulation of intramyocellular lipids, and insulin resistance. However, our previous research indicated that dyslipidemia in apolipoprotein E and low-density lipoprotein receptor double knock-out mice (ApoE/LDLR -/-) leads to improvement of exercise capacity. This study aimed to investigate in detail skeletal muscle function and metabolism in these dyslipidemic mice. We found that ApoE/LDLR -/- mice showed an increased grip strength as well as increased troponins, and Mhc2 levels in skeletal muscle. It was accompanied by the increased skeletal muscle mitochondria numbers (judged by increased citrate synthase activity) and elevated total adenine nucleotides pool. We noted increased triglycerides contents in skeletal muscles and increased serum free fatty acids (FFA) levels in ApoE/LDLR -/- mice. Importantly, Ranolazine mediated inhibition of FFA oxidation in ApoE/LDLR -/- mice led to the reduction of exercise capacity and total adenine nucleotides pool. Thus, this study demonstrated that increased capacity for fatty acid oxidation, an adaptive response to dyslipidemia leads to improved cellular energetics that translates to increased skeletal muscle strength and contributes to increased exercise capacity in ApoE/LDLR -/- mice.Marta TomczykAlicja BraczkoPatrycja JablonskaAdriana MikaKamil PrzyborowskiAgata JedrzejewskaOliwia KrolFilip KusTomasz SledzinskiStefan ChlopickiEwa M. SlominskaRyszard T. SmolenskiMDPI AGarticleskeletal musclemetabolic disordersdyslipidemiamitochondriaBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12251, p 12251 (2021)
institution DOAJ
collection DOAJ
language EN
topic skeletal muscle
metabolic disorders
dyslipidemia
mitochondria
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle skeletal muscle
metabolic disorders
dyslipidemia
mitochondria
Biology (General)
QH301-705.5
Chemistry
QD1-999
Marta Tomczyk
Alicja Braczko
Patrycja Jablonska
Adriana Mika
Kamil Przyborowski
Agata Jedrzejewska
Oliwia Krol
Filip Kus
Tomasz Sledzinski
Stefan Chlopicki
Ewa M. Slominska
Ryszard T. Smolenski
Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation
description Dyslipidemia is commonly linked to skeletal muscle dysfunction, accumulation of intramyocellular lipids, and insulin resistance. However, our previous research indicated that dyslipidemia in apolipoprotein E and low-density lipoprotein receptor double knock-out mice (ApoE/LDLR -/-) leads to improvement of exercise capacity. This study aimed to investigate in detail skeletal muscle function and metabolism in these dyslipidemic mice. We found that ApoE/LDLR -/- mice showed an increased grip strength as well as increased troponins, and Mhc2 levels in skeletal muscle. It was accompanied by the increased skeletal muscle mitochondria numbers (judged by increased citrate synthase activity) and elevated total adenine nucleotides pool. We noted increased triglycerides contents in skeletal muscles and increased serum free fatty acids (FFA) levels in ApoE/LDLR -/- mice. Importantly, Ranolazine mediated inhibition of FFA oxidation in ApoE/LDLR -/- mice led to the reduction of exercise capacity and total adenine nucleotides pool. Thus, this study demonstrated that increased capacity for fatty acid oxidation, an adaptive response to dyslipidemia leads to improved cellular energetics that translates to increased skeletal muscle strength and contributes to increased exercise capacity in ApoE/LDLR -/- mice.
format article
author Marta Tomczyk
Alicja Braczko
Patrycja Jablonska
Adriana Mika
Kamil Przyborowski
Agata Jedrzejewska
Oliwia Krol
Filip Kus
Tomasz Sledzinski
Stefan Chlopicki
Ewa M. Slominska
Ryszard T. Smolenski
author_facet Marta Tomczyk
Alicja Braczko
Patrycja Jablonska
Adriana Mika
Kamil Przyborowski
Agata Jedrzejewska
Oliwia Krol
Filip Kus
Tomasz Sledzinski
Stefan Chlopicki
Ewa M. Slominska
Ryszard T. Smolenski
author_sort Marta Tomczyk
title Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation
title_short Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation
title_full Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation
title_fullStr Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation
title_full_unstemmed Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation
title_sort enhanced muscle strength in dyslipidemic mice and its relation to increased capacity for fatty acid oxidation
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0b28bbcba6ba443abf9519a38c17710c
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