Differential Autophagy Response in Men and Women After Muscle Damage

Following muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentri...

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Main Authors: Hui-Ying Luk, Casey Appell, Danielle E. Levitt, Nigel C. Jiwan, Jakob L. Vingren
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.752347/full
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author Hui-Ying Luk
Casey Appell
Danielle E. Levitt
Danielle E. Levitt
Nigel C. Jiwan
Jakob L. Vingren
author_facet Hui-Ying Luk
Casey Appell
Danielle E. Levitt
Danielle E. Levitt
Nigel C. Jiwan
Jakob L. Vingren
author_sort Hui-Ying Luk
collection DOAJ
description Following muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentric exercise-induced muscle damage (EE) between untrained young men and women. Untrained men (n = 8, 22 ± 3 years) and women (n = 8, 19 ± 1 year) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either upper body resistance exercise (RE; designed to induce a hormonal response; EE + RE) or a time-matched rest period (20 min; EE + REST). Vastus lateralis biopsy samples were collected before (BL), and 12 h, and 24 h after RE/REST. Gene and protein expression levels of selective markers for autophagic initiation signaling, phagophore initiation, and elongation/sequestration were determined. Basal markers of autophagy were not different between sexes. For EE + RE, although initiation signaling (FOXO3) and autophagy-promoting (BECN1) genes were greater (p < 0.0001; 12.4-fold, p = 0.0010; 10.5-fold, respectively) for women than men, autophagic flux (LC3-II/LC3-I protein ratio) did not change for women and was lower (p < 0.0001 3.0-fold) than men. Furthermore, regardless of hormonal changes, LC3-I and LC3-II protein content decreased (p = 0.0090; 0.547-fold, p = 0.0410; 0.307-fold, respectively) for men suggesting increased LC3-I lipidation and autophagosome degradation whereas LC3-I protein content increased (p = 0.0360; 1.485-fold) for women suggesting decreased LC3-I lipidation. Collectively, our findings demonstrated basal autophagy was not different between men and women, did not change after EE alone, and was promoted with the acute hormonal increase after RE only in men but not in women. Thus, the autophagy response to moderate muscle damage is promoted by RE-induced hormonal changes in men only.
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spelling doaj.art-6e4b1f16cacb4345a4182f2b8a792fe92022-12-21T19:09:38ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-11-011210.3389/fphys.2021.752347752347Differential Autophagy Response in Men and Women After Muscle DamageHui-Ying Luk0Casey Appell1Danielle E. Levitt2Danielle E. Levitt3Nigel C. Jiwan4Jakob L. Vingren5Department of Kinesiology and Sports Management, Texas Tech University, Lubbock, TX, United StatesDepartment of Kinesiology and Sports Management, Texas Tech University, Lubbock, TX, United StatesDepartment of Kinesiology, Health Promotion, and Recreation, University of North Texas, Denton, TX, United StatesDepartment of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, United StatesDepartment of Kinesiology and Sports Management, Texas Tech University, Lubbock, TX, United StatesDepartment of Kinesiology, Health Promotion, and Recreation, University of North Texas, Denton, TX, United StatesFollowing muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentric exercise-induced muscle damage (EE) between untrained young men and women. Untrained men (n = 8, 22 ± 3 years) and women (n = 8, 19 ± 1 year) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either upper body resistance exercise (RE; designed to induce a hormonal response; EE + RE) or a time-matched rest period (20 min; EE + REST). Vastus lateralis biopsy samples were collected before (BL), and 12 h, and 24 h after RE/REST. Gene and protein expression levels of selective markers for autophagic initiation signaling, phagophore initiation, and elongation/sequestration were determined. Basal markers of autophagy were not different between sexes. For EE + RE, although initiation signaling (FOXO3) and autophagy-promoting (BECN1) genes were greater (p < 0.0001; 12.4-fold, p = 0.0010; 10.5-fold, respectively) for women than men, autophagic flux (LC3-II/LC3-I protein ratio) did not change for women and was lower (p < 0.0001 3.0-fold) than men. Furthermore, regardless of hormonal changes, LC3-I and LC3-II protein content decreased (p = 0.0090; 0.547-fold, p = 0.0410; 0.307-fold, respectively) for men suggesting increased LC3-I lipidation and autophagosome degradation whereas LC3-I protein content increased (p = 0.0360; 1.485-fold) for women suggesting decreased LC3-I lipidation. Collectively, our findings demonstrated basal autophagy was not different between men and women, did not change after EE alone, and was promoted with the acute hormonal increase after RE only in men but not in women. Thus, the autophagy response to moderate muscle damage is promoted by RE-induced hormonal changes in men only.https://www.frontiersin.org/articles/10.3389/fphys.2021.752347/fullcortisolgrowth hormoneLC3-II/LC3-I ratiomacroautophagysex dimorphism
spellingShingle Hui-Ying Luk
Casey Appell
Danielle E. Levitt
Danielle E. Levitt
Nigel C. Jiwan
Jakob L. Vingren
Differential Autophagy Response in Men and Women After Muscle Damage
Frontiers in Physiology
cortisol
growth hormone
LC3-II/LC3-I ratio
macroautophagy
sex dimorphism
title Differential Autophagy Response in Men and Women After Muscle Damage
title_full Differential Autophagy Response in Men and Women After Muscle Damage
title_fullStr Differential Autophagy Response in Men and Women After Muscle Damage
title_full_unstemmed Differential Autophagy Response in Men and Women After Muscle Damage
title_short Differential Autophagy Response in Men and Women After Muscle Damage
title_sort differential autophagy response in men and women after muscle damage
topic cortisol
growth hormone
LC3-II/LC3-I ratio
macroautophagy
sex dimorphism
url https://www.frontiersin.org/articles/10.3389/fphys.2021.752347/full
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