Loading…
Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease
Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by...
Saved in:
| Published in: | The Journal of physiology 2023-02, Vol.601 (3), p.551-566 |
|---|---|
| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c4407-c8e4ee5efeb3bde23089736fba01b8165037f7e789ecace79c2b7abf6a5c951d3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c4407-c8e4ee5efeb3bde23089736fba01b8165037f7e789ecace79c2b7abf6a5c951d3 |
| container_end_page | 566 |
| container_issue | 3 |
| container_start_page | 551 |
| container_title | The Journal of physiology |
| container_volume | 601 |
| creator | Rodriguez‐Lopez, Carlos Santalla, Alfredo Valenzuela, Pedro. L Real‐Martínez, Alberto Villarreal‐Salazar, Mónica Rodriguez‐Gomez, Irene Pinós, Tomàs Ara, Ignacio Lucia, Alejandro |
| description | Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild‐type male mice. Peak oxygen uptake (V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate‐associated workload were determined by indirect calorimetry during an incremental cycle‐ergometer test. Despite having a much lower V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg−1 min−1, respectively; P |
| doi_str_mv | 10.1113/JP283743 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10099855</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2771204513</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4407-c8e4ee5efeb3bde23089736fba01b8165037f7e789ecace79c2b7abf6a5c951d3</originalsourceid><addsrcrecordid>eNp1kc1O3TAQha2qVbnQSn2CylI3bELtTBwn3VQI9QcEKgu6thx7Eox8bWonlPv2NeK3SKxmMZ8-nZlDyAfO9jjn8PnotO5ANvCKrHjT9pWUPbwmK8bqugIp-BbZzvmCMQ6s79-SLWhBMpB8RezJko1HOvmNiRMGugR9pZ3Xg_Nu3lAdLB31TOO1s3p2MdCkZ6R2SS5MFK8xGZfxCz0M2U3nc6Zjimt6YvaTLVZbdjrjO_Jm1D7j-7u5Q35__3Z28LM6_vXj8GD_uDJNw2RlOmwQBY44wGCxBtb1Etpx0IwPHW9FiTxKlF2PRhuUvakHqYex1cL0glvYIV9vvZfLsEZrMMxJe3WZ3FqnjYraqf83wZ2rKV4pzspfOiGKYffOkOKfBfOs1i4b9F4HjEtWtQTRtUI0bUE_PUMv4pJCua9QktesERwehSbFnBOOD2k4UzfdqfvuCvrxafoH8L6sAuzdAn-dx82LInV2dMoFCAn_AIdWo9U</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2771204513</pqid></control><display><type>article</type><title>Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Rodriguez‐Lopez, Carlos ; Santalla, Alfredo ; Valenzuela, Pedro. L ; Real‐Martínez, Alberto ; Villarreal‐Salazar, Mónica ; Rodriguez‐Gomez, Irene ; Pinós, Tomàs ; Ara, Ignacio ; Lucia, Alejandro</creator><creatorcontrib>Rodriguez‐Lopez, Carlos ; Santalla, Alfredo ; Valenzuela, Pedro. L ; Real‐Martínez, Alberto ; Villarreal‐Salazar, Mónica ; Rodriguez‐Gomez, Irene ; Pinós, Tomàs ; Ara, Ignacio ; Lucia, Alejandro</creatorcontrib><description>Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild‐type male mice. Peak oxygen uptake (V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate‐associated workload were determined by indirect calorimetry during an incremental cycle‐ergometer test. Despite having a much lower V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg−1 min−1, respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min−1, P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$, P < 0.0001) and MFO rate‐associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg−1, P = 0.020) than controls. No between‐group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near‐maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease.
Key points
Physically active McArdle patients show an exceptional fat oxidation capacity.
Maximal fat oxidation rate occurs near‐maximal exercise capacity in these patients.
McArdle patients’ exercise tolerance might rely on maximal fat oxidation rate capacity.
Hyperpnoea might cloud substrate oxidation measurements in some patients.
An animal model revealed overall no higher molecular markers of lipid transport/metabolism.
figure legend McArdle disease is caused by inherited blockade of glycogen breakdown in skeletal muscle fibres, with subsequent intolerance to most exercise tasks, as well as a substantial impairment of peak aerobic capacity. The present study indicates that the exercise capacity of these patients is mainly sustained by fat oxidation, with active patients showing an exceptional maximal fat oxidation rate (comparable to athletes) during endurance exercise, possibly as an adaptation to muscle glycogen unavailability. On the other hand, data in the (untrained) mouse model of the disease revealed overall no major differences at baseline in molecular markers of lipid transport/metabolism compared to wild‐type mice.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/JP283743</identifier><identifier>PMID: 36370371</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adipose tissue ; Adipose Tissue - metabolism ; anaplerotic ; Animal models ; Animals ; Calorimetry ; Carbohydrate metabolism ; Exercise ; Exercise Test ; Fat metabolism ; fatty acids ; Female ; Glycogen ; Glycogen - metabolism ; glycogen depletion ; Glycogen Storage Disease Type V - metabolism ; glycogen store disease ; lactate ; Lipid metabolism ; Lipids ; Male ; Metabolism ; Mice ; muscle fatigue ; Muscle, Skeletal - physiology ; Oxidation ; Oxidation-Reduction ; Oxygen Consumption - physiology ; Skeletal muscle ; substrate oxidation ; tricarboxylic acid cycle ; Workloads</subject><ispartof>The Journal of physiology, 2023-02, Vol.601 (3), p.551-566</ispartof><rights>2022 The Authors. published by John Wiley & Sons Ltd on behalf of The Physiological Society.</rights><rights>2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4407-c8e4ee5efeb3bde23089736fba01b8165037f7e789ecace79c2b7abf6a5c951d3</citedby><cites>FETCH-LOGICAL-c4407-c8e4ee5efeb3bde23089736fba01b8165037f7e789ecace79c2b7abf6a5c951d3</cites><orcidid>0000-0002-1622-7109 ; 0000-0002-2854-6684</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36370371$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodriguez‐Lopez, Carlos</creatorcontrib><creatorcontrib>Santalla, Alfredo</creatorcontrib><creatorcontrib>Valenzuela, Pedro. L</creatorcontrib><creatorcontrib>Real‐Martínez, Alberto</creatorcontrib><creatorcontrib>Villarreal‐Salazar, Mónica</creatorcontrib><creatorcontrib>Rodriguez‐Gomez, Irene</creatorcontrib><creatorcontrib>Pinós, Tomàs</creatorcontrib><creatorcontrib>Ara, Ignacio</creatorcontrib><creatorcontrib>Lucia, Alejandro</creatorcontrib><title>Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild‐type male mice. Peak oxygen uptake (V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate‐associated workload were determined by indirect calorimetry during an incremental cycle‐ergometer test. Despite having a much lower V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg−1 min−1, respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min−1, P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$, P < 0.0001) and MFO rate‐associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg−1, P = 0.020) than controls. No between‐group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near‐maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease.
Key points
Physically active McArdle patients show an exceptional fat oxidation capacity.
Maximal fat oxidation rate occurs near‐maximal exercise capacity in these patients.
McArdle patients’ exercise tolerance might rely on maximal fat oxidation rate capacity.
Hyperpnoea might cloud substrate oxidation measurements in some patients.
An animal model revealed overall no higher molecular markers of lipid transport/metabolism.
figure legend McArdle disease is caused by inherited blockade of glycogen breakdown in skeletal muscle fibres, with subsequent intolerance to most exercise tasks, as well as a substantial impairment of peak aerobic capacity. The present study indicates that the exercise capacity of these patients is mainly sustained by fat oxidation, with active patients showing an exceptional maximal fat oxidation rate (comparable to athletes) during endurance exercise, possibly as an adaptation to muscle glycogen unavailability. On the other hand, data in the (untrained) mouse model of the disease revealed overall no major differences at baseline in molecular markers of lipid transport/metabolism compared to wild‐type mice.</description><subject>Adipose tissue</subject><subject>Adipose Tissue - metabolism</subject><subject>anaplerotic</subject><subject>Animal models</subject><subject>Animals</subject><subject>Calorimetry</subject><subject>Carbohydrate metabolism</subject><subject>Exercise</subject><subject>Exercise Test</subject><subject>Fat metabolism</subject><subject>fatty acids</subject><subject>Female</subject><subject>Glycogen</subject><subject>Glycogen - metabolism</subject><subject>glycogen depletion</subject><subject>Glycogen Storage Disease Type V - metabolism</subject><subject>glycogen store disease</subject><subject>lactate</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Male</subject><subject>Metabolism</subject><subject>Mice</subject><subject>muscle fatigue</subject><subject>Muscle, Skeletal - physiology</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Oxygen Consumption - physiology</subject><subject>Skeletal muscle</subject><subject>substrate oxidation</subject><subject>tricarboxylic acid cycle</subject><subject>Workloads</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp1kc1O3TAQha2qVbnQSn2CylI3bELtTBwn3VQI9QcEKgu6thx7Eox8bWonlPv2NeK3SKxmMZ8-nZlDyAfO9jjn8PnotO5ANvCKrHjT9pWUPbwmK8bqugIp-BbZzvmCMQ6s79-SLWhBMpB8RezJko1HOvmNiRMGugR9pZ3Xg_Nu3lAdLB31TOO1s3p2MdCkZ6R2SS5MFK8xGZfxCz0M2U3nc6Zjimt6YvaTLVZbdjrjO_Jm1D7j-7u5Q35__3Z28LM6_vXj8GD_uDJNw2RlOmwQBY44wGCxBtb1Etpx0IwPHW9FiTxKlF2PRhuUvakHqYex1cL0glvYIV9vvZfLsEZrMMxJe3WZ3FqnjYraqf83wZ2rKV4pzspfOiGKYffOkOKfBfOs1i4b9F4HjEtWtQTRtUI0bUE_PUMv4pJCua9QktesERwehSbFnBOOD2k4UzfdqfvuCvrxafoH8L6sAuzdAn-dx82LInV2dMoFCAn_AIdWo9U</recordid><startdate>20230201</startdate><enddate>20230201</enddate><creator>Rodriguez‐Lopez, Carlos</creator><creator>Santalla, Alfredo</creator><creator>Valenzuela, Pedro. L</creator><creator>Real‐Martínez, Alberto</creator><creator>Villarreal‐Salazar, Mónica</creator><creator>Rodriguez‐Gomez, Irene</creator><creator>Pinós, Tomàs</creator><creator>Ara, Ignacio</creator><creator>Lucia, Alejandro</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1622-7109</orcidid><orcidid>https://orcid.org/0000-0002-2854-6684</orcidid></search><sort><creationdate>20230201</creationdate><title>Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease</title><author>Rodriguez‐Lopez, Carlos ; Santalla, Alfredo ; Valenzuela, Pedro. L ; Real‐Martínez, Alberto ; Villarreal‐Salazar, Mónica ; Rodriguez‐Gomez, Irene ; Pinós, Tomàs ; Ara, Ignacio ; Lucia, Alejandro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4407-c8e4ee5efeb3bde23089736fba01b8165037f7e789ecace79c2b7abf6a5c951d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue - metabolism</topic><topic>anaplerotic</topic><topic>Animal models</topic><topic>Animals</topic><topic>Calorimetry</topic><topic>Carbohydrate metabolism</topic><topic>Exercise</topic><topic>Exercise Test</topic><topic>Fat metabolism</topic><topic>fatty acids</topic><topic>Female</topic><topic>Glycogen</topic><topic>Glycogen - metabolism</topic><topic>glycogen depletion</topic><topic>Glycogen Storage Disease Type V - metabolism</topic><topic>glycogen store disease</topic><topic>lactate</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Male</topic><topic>Metabolism</topic><topic>Mice</topic><topic>muscle fatigue</topic><topic>Muscle, Skeletal - physiology</topic><topic>Oxidation</topic><topic>Oxidation-Reduction</topic><topic>Oxygen Consumption - physiology</topic><topic>Skeletal muscle</topic><topic>substrate oxidation</topic><topic>tricarboxylic acid cycle</topic><topic>Workloads</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodriguez‐Lopez, Carlos</creatorcontrib><creatorcontrib>Santalla, Alfredo</creatorcontrib><creatorcontrib>Valenzuela, Pedro. L</creatorcontrib><creatorcontrib>Real‐Martínez, Alberto</creatorcontrib><creatorcontrib>Villarreal‐Salazar, Mónica</creatorcontrib><creatorcontrib>Rodriguez‐Gomez, Irene</creatorcontrib><creatorcontrib>Pinós, Tomàs</creatorcontrib><creatorcontrib>Ara, Ignacio</creatorcontrib><creatorcontrib>Lucia, Alejandro</creatorcontrib><collection>Wiley Online Library website</collection><collection>Wiley Online Library Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodriguez‐Lopez, Carlos</au><au>Santalla, Alfredo</au><au>Valenzuela, Pedro. L</au><au>Real‐Martínez, Alberto</au><au>Villarreal‐Salazar, Mónica</au><au>Rodriguez‐Gomez, Irene</au><au>Pinós, Tomàs</au><au>Ara, Ignacio</au><au>Lucia, Alejandro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>601</volume><issue>3</issue><spage>551</spage><epage>566</epage><pages>551-566</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild‐type male mice. Peak oxygen uptake (V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate‐associated workload were determined by indirect calorimetry during an incremental cycle‐ergometer test. Despite having a much lower V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg−1 min−1, respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min−1, P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V̇O2peak${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}$, P < 0.0001) and MFO rate‐associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg−1, P = 0.020) than controls. No between‐group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near‐maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease.
Key points
Physically active McArdle patients show an exceptional fat oxidation capacity.
Maximal fat oxidation rate occurs near‐maximal exercise capacity in these patients.
McArdle patients’ exercise tolerance might rely on maximal fat oxidation rate capacity.
Hyperpnoea might cloud substrate oxidation measurements in some patients.
An animal model revealed overall no higher molecular markers of lipid transport/metabolism.
figure legend McArdle disease is caused by inherited blockade of glycogen breakdown in skeletal muscle fibres, with subsequent intolerance to most exercise tasks, as well as a substantial impairment of peak aerobic capacity. The present study indicates that the exercise capacity of these patients is mainly sustained by fat oxidation, with active patients showing an exceptional maximal fat oxidation rate (comparable to athletes) during endurance exercise, possibly as an adaptation to muscle glycogen unavailability. On the other hand, data in the (untrained) mouse model of the disease revealed overall no major differences at baseline in molecular markers of lipid transport/metabolism compared to wild‐type mice.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36370371</pmid><doi>10.1113/JP283743</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1622-7109</orcidid><orcidid>https://orcid.org/0000-0002-2854-6684</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3751 |
| ispartof | The Journal of physiology, 2023-02, Vol.601 (3), p.551-566 |
| issn | 0022-3751 1469-7793 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10099855 |
| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Adipose tissue Adipose Tissue - metabolism anaplerotic Animal models Animals Calorimetry Carbohydrate metabolism Exercise Exercise Test Fat metabolism fatty acids Female Glycogen Glycogen - metabolism glycogen depletion Glycogen Storage Disease Type V - metabolism glycogen store disease lactate Lipid metabolism Lipids Male Metabolism Mice muscle fatigue Muscle, Skeletal - physiology Oxidation Oxidation-Reduction Oxygen Consumption - physiology Skeletal muscle substrate oxidation tricarboxylic acid cycle Workloads |
| title | Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T18%3A08%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Muscle%20glycogen%20unavailability%20and%20fat%20oxidation%20rate%20during%20exercise:%20Insights%20from%20McArdle%20disease&rft.jtitle=The%20Journal%20of%20physiology&rft.au=Rodriguez%E2%80%90Lopez,%20Carlos&rft.date=2023-02-01&rft.volume=601&rft.issue=3&rft.spage=551&rft.epage=566&rft.pages=551-566&rft.issn=0022-3751&rft.eissn=1469-7793&rft_id=info:doi/10.1113/JP283743&rft_dat=%3Cproquest_pubme%3E2771204513%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4407-c8e4ee5efeb3bde23089736fba01b8165037f7e789ecace79c2b7abf6a5c951d3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2771204513&rft_id=info:pmid/36370371&rfr_iscdi=true |