Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats.
Emerging evidence suggests the potential of rapamycin, an antibiotic from Streptomyces hygroscopicus that functions as a mechanistic target of rapamycin (mTOR) inhibitor, as a mimetic of caloric restriction (CR) for maintaining skeletal muscle health. Several studies showed that rapamycin administra...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0312859 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850245839309504512 |
|---|---|
| author | Satoru Ato Chieri Oya Riki Ogasawara |
| author_facet | Satoru Ato Chieri Oya Riki Ogasawara |
| author_sort | Satoru Ato |
| collection | DOAJ |
| description | Emerging evidence suggests the potential of rapamycin, an antibiotic from Streptomyces hygroscopicus that functions as a mechanistic target of rapamycin (mTOR) inhibitor, as a mimetic of caloric restriction (CR) for maintaining skeletal muscle health. Several studies showed that rapamycin administration (RAP) reduced appetite and energy intake. However, the physiological and molecular differences between RAP and CR in skeletal muscle are not fully understood. Here we observed the effects of 4 weeks of RAP administration and CR corresponding to the reduction in energy intake produced by RAP administration (PF, paired feeding) on fast glycolytic and slow oxidative muscle in young adult rats. We found that 4 weeks of RAP demonstrated low fast-glycolytic muscle mass with smaller type I and IIb/x myofiber size independent of the energy intake. In addition, PF improved the contractile function of the plantar flexor muscle, whereas RAP did not improve its function. The suppressing response of mTORC1 signaling to RAP is greater in slow-oxidative muscles than in fast-glycolytic muscles. In addition, systemic glucose tolerance was exacerbated by RAP, with reduced expression of Rictor and hexokinase in skeletal muscle. These observations imply that RAP may have a slight but significant negative impact and it obviously different to CR in young adult skeletal muscle. |
| format | Article |
| id | doaj-art-32cac8d3e9ec4cbd962da2c64e912575 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-32cac8d3e9ec4cbd962da2c64e9125752025-08-20T01:59:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031285910.1371/journal.pone.0312859Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats.Satoru AtoChieri OyaRiki OgasawaraEmerging evidence suggests the potential of rapamycin, an antibiotic from Streptomyces hygroscopicus that functions as a mechanistic target of rapamycin (mTOR) inhibitor, as a mimetic of caloric restriction (CR) for maintaining skeletal muscle health. Several studies showed that rapamycin administration (RAP) reduced appetite and energy intake. However, the physiological and molecular differences between RAP and CR in skeletal muscle are not fully understood. Here we observed the effects of 4 weeks of RAP administration and CR corresponding to the reduction in energy intake produced by RAP administration (PF, paired feeding) on fast glycolytic and slow oxidative muscle in young adult rats. We found that 4 weeks of RAP demonstrated low fast-glycolytic muscle mass with smaller type I and IIb/x myofiber size independent of the energy intake. In addition, PF improved the contractile function of the plantar flexor muscle, whereas RAP did not improve its function. The suppressing response of mTORC1 signaling to RAP is greater in slow-oxidative muscles than in fast-glycolytic muscles. In addition, systemic glucose tolerance was exacerbated by RAP, with reduced expression of Rictor and hexokinase in skeletal muscle. These observations imply that RAP may have a slight but significant negative impact and it obviously different to CR in young adult skeletal muscle.https://doi.org/10.1371/journal.pone.0312859 |
| spellingShingle | Satoru Ato Chieri Oya Riki Ogasawara Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats. PLoS ONE |
| title | Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats. |
| title_full | Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats. |
| title_fullStr | Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats. |
| title_full_unstemmed | Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats. |
| title_short | Rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle Rictor, the mTORC2 component, expression independent of energy intake in young rats. |
| title_sort | rapamycin administration causes a decrease in muscle contractile function and systemic glucose intolerance concomitant with reduced skeletal muscle rictor the mtorc2 component expression independent of energy intake in young rats |
| url | https://doi.org/10.1371/journal.pone.0312859 |
| work_keys_str_mv | AT satoruato rapamycinadministrationcausesadecreaseinmusclecontractilefunctionandsystemicglucoseintoleranceconcomitantwithreducedskeletalmusclerictorthemtorc2componentexpressionindependentofenergyintakeinyoungrats AT chierioya rapamycinadministrationcausesadecreaseinmusclecontractilefunctionandsystemicglucoseintoleranceconcomitantwithreducedskeletalmusclerictorthemtorc2componentexpressionindependentofenergyintakeinyoungrats AT rikiogasawara rapamycinadministrationcausesadecreaseinmusclecontractilefunctionandsystemicglucoseintoleranceconcomitantwithreducedskeletalmusclerictorthemtorc2componentexpressionindependentofenergyintakeinyoungrats |