Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome
Women with polycystic ovary syndrome (PCOS) are reported to have greater lean mass and insulin resistance. To examine muscular changes in a prenatally androgenized (PNA) rat model for PCOS, Sprague–Dawley rats were exposed to 5 mg testosterone or vehicle daily on gestational days 16–19. At 15 weeks...
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doaj-dfa8e413df6d4f1695cfd43c0996ca7f2020-11-25T03:56:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-01217918791810.3390/ijms21217918Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary SyndromeAuryana DeChick0Rebecca Hetz1Jack Lee2Diana L. Speelman3Department of Biochemistry, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USADepartment of Biochemistry, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USADepartment of Biochemistry, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USADepartment of Biochemistry, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USAWomen with polycystic ovary syndrome (PCOS) are reported to have greater lean mass and insulin resistance. To examine muscular changes in a prenatally androgenized (PNA) rat model for PCOS, Sprague–Dawley rats were exposed to 5 mg testosterone or vehicle daily on gestational days 16–19. At 15 weeks of age, endurance on a rota-rod treadmill was measured. At 16 weeks of age, fasting blood glucose and insulin, hindlimb skeletal muscle mass, muscle fiber cross-sectional area (CSA) and composition, and intra- and peri-muscular lipid droplets were examined. Expression of mitochondrial marker ATP synthase and insulin signaling proteins were also investigated. Compared with controls, PNA female rats demonstrated greater total body and hindlimb muscle weights, greater muscle fiber CSA, and trending reduced time on the rota-rod. An increase in fibers co-expressing the slow and fast isoforms of myosin (90 vs. 86%, <i>p</i> < 0.05) and greater expression of ATP synthase (6-fold, <i>p</i> < 0.005) were observed in the gastrocnemius (GN) muscle. More lipid content was observed in GN and tibialis anterior (TA) muscles. PNA rats had elevated fasting serum insulin (1.9 vs. 1.2 ng/mL, <i>p</i> < 0.005) but comparable fasting glucose. Expression of total and Ser<sup>636/9</sup>-phosphorylated IRS1 were altered in PNA rat hindlimb muscles. Together, skeletal muscle alterations in hindlimb muscles of a PNA rat model for PCOS may represent consequences of, or adaptations to, insulin resistance in this model.https://www.mdpi.com/1422-0067/21/21/7918hyperandrogenemiamuscle fiber typemuscle cross-sectional areaintra-muscular lipidsperi-muscular lipidsPCOS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Auryana DeChick Rebecca Hetz Jack Lee Diana L. Speelman |
spellingShingle |
Auryana DeChick Rebecca Hetz Jack Lee Diana L. Speelman Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome International Journal of Molecular Sciences hyperandrogenemia muscle fiber type muscle cross-sectional area intra-muscular lipids peri-muscular lipids PCOS |
author_facet |
Auryana DeChick Rebecca Hetz Jack Lee Diana L. Speelman |
author_sort |
Auryana DeChick |
title |
Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome |
title_short |
Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome |
title_full |
Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome |
title_fullStr |
Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome |
title_full_unstemmed |
Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome |
title_sort |
increased skeletal muscle fiber cross-sectional area, muscle phenotype shift, and altered insulin signaling in rat hindlimb muscles in a prenatally androgenized rat model for polycystic ovary syndrome |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-10-01 |
description |
Women with polycystic ovary syndrome (PCOS) are reported to have greater lean mass and insulin resistance. To examine muscular changes in a prenatally androgenized (PNA) rat model for PCOS, Sprague–Dawley rats were exposed to 5 mg testosterone or vehicle daily on gestational days 16–19. At 15 weeks of age, endurance on a rota-rod treadmill was measured. At 16 weeks of age, fasting blood glucose and insulin, hindlimb skeletal muscle mass, muscle fiber cross-sectional area (CSA) and composition, and intra- and peri-muscular lipid droplets were examined. Expression of mitochondrial marker ATP synthase and insulin signaling proteins were also investigated. Compared with controls, PNA female rats demonstrated greater total body and hindlimb muscle weights, greater muscle fiber CSA, and trending reduced time on the rota-rod. An increase in fibers co-expressing the slow and fast isoforms of myosin (90 vs. 86%, <i>p</i> < 0.05) and greater expression of ATP synthase (6-fold, <i>p</i> < 0.005) were observed in the gastrocnemius (GN) muscle. More lipid content was observed in GN and tibialis anterior (TA) muscles. PNA rats had elevated fasting serum insulin (1.9 vs. 1.2 ng/mL, <i>p</i> < 0.005) but comparable fasting glucose. Expression of total and Ser<sup>636/9</sup>-phosphorylated IRS1 were altered in PNA rat hindlimb muscles. Together, skeletal muscle alterations in hindlimb muscles of a PNA rat model for PCOS may represent consequences of, or adaptations to, insulin resistance in this model. |
topic |
hyperandrogenemia muscle fiber type muscle cross-sectional area intra-muscular lipids peri-muscular lipids PCOS |
url |
https://www.mdpi.com/1422-0067/21/21/7918 |
work_keys_str_mv |
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