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Deletion of muscle Igf1 exacerbates disuse atrophy weakness in mice.

Deletion of muscle Igf1 exacerbates disuse atrophy weakness in mice.

Authors :
Spradlin RA
Vassilakos G
Matheny MK
Jones NC
Goldman JL
Lei H
Barton ER
Source :
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2021 Sep 01; Vol. 131 (3), pp. 881-894. Date of Electronic Publication: 2021 Jul 22.
Publication Year :
2021

Abstract

Muscle atrophy occurs as a result of prolonged periods of reduced mechanical stimulation associated with injury or disease. The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and load sensing pathways can both aid in recovery from disuse through their shared downstream signaling, but their relative contributions to these processes are not fully understood. The goal of this study was to determine whether reduced muscle IGF-1 altered the response to disuse and reloading. Adult male mice with inducible muscle-specific IGF-1 deletion (MID) induced 1 wk before suspension and age-matched controls (CON) were subjected to hindlimb suspension and reloading. Analysis of muscle force, morphology, gene expression, signaling, and tissue weights was performed in nonsuspended (NS) mice, and those suspended for 7 days or reloaded following suspension for 3, 7, and 14 days. MID mice displayed diminished IGF-1 protein levels and muscle atrophy before suspension. Muscles from suspended CON mice displayed a similar extent of atrophy and depletion of IGF-1, yet combined loss of load and IGF-1 was not additive with respect to muscle mass. In contrast, soleus force generation capacity was diminished to the greatest extent when both suspension and IGF-1 deletion occurred. Recovery of mass, force, and gene expression patterns following suspension were similar in CON and MID mice, even though IGF-1 levels increased only in muscles from CON mice. Diminished strength in disuse atrophy is exacerbated with the loss of muscle IGF-1 production, whereas recovery of mass and strength upon reloading can occur even IGF-1 is low. NEW & NOTEWORTHY A mouse model with skeletal muscle-specific inducible deletion of Igf1 was used to address the importance of this growth factor for the consequences of disuse atrophy. Rapid and equivalent loss of IGF-I and mass occurred with deletion or disuse. Decrements in strength were most severe with combined loss of load and IGF-1. Return of mass and strength upon reloading was independent of IGF-1.

Details

Language :
English
ISSN :
1522-1601
Volume :
131
Issue :
3
Database :
MEDLINE
Journal :
Journal of applied physiology (Bethesda, Md. : 1985)
Publication Type :
Academic Journal
Accession number :
34292789
Full Text :
https://doi.org/10.1152/japplphysiol.00090.2021