Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity

Abstract This study aimed to compare the protein content of pathways related to mTORC1 signaling and oxidative metabolism in whole skeletal muscle and isolated muscle fibers from healthy individuals (HEALTHY) and individuals with obesity (OBESE). Muscle biopsies were obtained from 18 individuals. Sa...

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Main Authors: Cristian Campos, Marcelo Flores-Opazo, Denisse Valladares-Ide, Claudio Cabello-Verrugio, Pilar Parada, Francisco Morales, Joseline Arredondo, Luis Peñailillo
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-09169-7
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author Cristian Campos
Marcelo Flores-Opazo
Denisse Valladares-Ide
Claudio Cabello-Verrugio
Pilar Parada
Francisco Morales
Joseline Arredondo
Luis Peñailillo
author_facet Cristian Campos
Marcelo Flores-Opazo
Denisse Valladares-Ide
Claudio Cabello-Verrugio
Pilar Parada
Francisco Morales
Joseline Arredondo
Luis Peñailillo
author_sort Cristian Campos
collection DOAJ
description Abstract This study aimed to compare the protein content of pathways related to mTORC1 signaling and oxidative metabolism in whole skeletal muscle and isolated muscle fibers from healthy individuals (HEALTHY) and individuals with obesity (OBESE). Muscle biopsies were obtained from 18 individuals. Samples were freeze-dried, and fibers were isolated and fiber-typed for type I and IIa myosin heavy chain isoforms. The protein content of Akt-1, mTOR, p70s6K, S6 ribosomal protein (S6RP), ERK1/2, p38, total protein ubiquitination (TPU), and OXPHOS proteins in whole muscle and isolated fibers was determined using immunoblotting. Muscle fiber morphology was also assessed. Fiber type proportion was similar in HEALTHY, while OBESE showed a greater proportion of type IIa fibers. Fiber cross-sectional area (CSA) was similar in HEALTHY, while OBESE showed greater CSA of type I fibers. Protein content of p70s6K was lower (73%, p = 0.008), while ERK1/2 (29%, p = 0.05) and TPU (32%, p = 0.03) were increased in whole muscle from OBESE compared with HEALTHY. Fiber-specific differences were found in p38 (IIa > I, p = 0.03) in HEALTHY, while OBESE showed different complex II and V (I > IIa, p = 0.03 and p = 0.04, respectively) between fibers. Furthermore, a negative correlation was found between body mass and p70s6K protein content. Our findings suggest that obesity impairs the mTORC1-related protein pathway while increasing degradation in individuals with obesity.
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spelling doaj-art-8b2978a416014be5b148f2c4bcaca1b22025-08-20T04:01:26ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-09169-7Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesityCristian Campos0Marcelo Flores-Opazo1Denisse Valladares-Ide2Claudio Cabello-Verrugio3Pilar Parada4Francisco Morales5Joseline Arredondo6Luis Peñailillo7Exercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, School of Physical Therapy, Universidad Andres BelloExercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, School of Physical Therapy, Universidad Andres BelloLong Active Life Laboratory, Instituto de Ciencias de la Salud, Universidad de O’HigginsCenter for Research on Pandemic Resilience, Faculty of Life Sciences and Institute of Public Health, Universidad Andres BelloCentro de Biotecnología de Sistemas, Universidad Andres BelloEspecialidad en Medicina del Deporte y la Actividad Física, Facultad de Ciencias Médicas, Universidad De SantiagoExercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, School of Physical Therapy, Universidad Andres BelloExercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, School of Physical Therapy, Universidad Andres BelloAbstract This study aimed to compare the protein content of pathways related to mTORC1 signaling and oxidative metabolism in whole skeletal muscle and isolated muscle fibers from healthy individuals (HEALTHY) and individuals with obesity (OBESE). Muscle biopsies were obtained from 18 individuals. Samples were freeze-dried, and fibers were isolated and fiber-typed for type I and IIa myosin heavy chain isoforms. The protein content of Akt-1, mTOR, p70s6K, S6 ribosomal protein (S6RP), ERK1/2, p38, total protein ubiquitination (TPU), and OXPHOS proteins in whole muscle and isolated fibers was determined using immunoblotting. Muscle fiber morphology was also assessed. Fiber type proportion was similar in HEALTHY, while OBESE showed a greater proportion of type IIa fibers. Fiber cross-sectional area (CSA) was similar in HEALTHY, while OBESE showed greater CSA of type I fibers. Protein content of p70s6K was lower (73%, p = 0.008), while ERK1/2 (29%, p = 0.05) and TPU (32%, p = 0.03) were increased in whole muscle from OBESE compared with HEALTHY. Fiber-specific differences were found in p38 (IIa > I, p = 0.03) in HEALTHY, while OBESE showed different complex II and V (I > IIa, p = 0.03 and p = 0.04, respectively) between fibers. Furthermore, a negative correlation was found between body mass and p70s6K protein content. Our findings suggest that obesity impairs the mTORC1-related protein pathway while increasing degradation in individuals with obesity.https://doi.org/10.1038/s41598-025-09169-7Skeletal muscleMuscle ubiquitinationMuscle protein synthesisMitochondrial complexOverweight
spellingShingle Cristian Campos
Marcelo Flores-Opazo
Denisse Valladares-Ide
Claudio Cabello-Verrugio
Pilar Parada
Francisco Morales
Joseline Arredondo
Luis Peñailillo
Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity
Scientific Reports
Skeletal muscle
Muscle ubiquitination
Muscle protein synthesis
Mitochondrial complex
Overweight
title Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity
title_full Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity
title_fullStr Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity
title_full_unstemmed Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity
title_short Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity
title_sort fiber specific differences in protein content of pathways related to mtorc1 signaling and oxidative metabolism in individuals with obesity
topic Skeletal muscle
Muscle ubiquitination
Muscle protein synthesis
Mitochondrial complex
Overweight
url https://doi.org/10.1038/s41598-025-09169-7
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