Deletion of muscle Igf1 exacerbates disuse atrophy weakness in mice

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 if reduced muscle IGF-1 altered the response to disuse and reloading. Adult male mice with inducible muscle-specific IGF-1 deletion (MID) induced 1 week 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 were performed in non-suspended 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 prior to 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.

Circadian regulation in aging: Implications for spaceflight and life on earth

“…The loss of muscle strength was greatest in Igf1-deleted mice following disuse. The return of muscle mass and strength in recovery seemed independent of Igf1 concluding Igf1 as one of the key players in muscle degradation (Spradlin et al, 2021). Vogel et al…”

“…The loss of muscle strength was greatest in Igf1 ‐deleted mice following disuse. The return of muscle mass and strength in recovery seemed independent of Igf1 concluding Igf1 as one of the key players in muscle degradation (Spradlin et al, 2021 ). Vogel et al reports on human cells (Jurkat T‐cells, U937) that were exposed to altered gravity within short duration gravitational transitions in parabolic flight (Vogel et al, 2019 ).…”

Lean nonalcoholic fatty liver disease and sarcopenia

“…In addition, adiponectin plays the role of anti-inflammatory by inhibiting TNFa, improving liver steatosis and inflammation (102,103). Fat accumulation and aging damage the signaling pathway of the GH/ IGF-1 axis, leading to decreased levels of muscle synthesis (104, 105). In an animal model, NAFLD is reported to be associated with decreased muscle mass and strength as well as decreased IGF-1 levels, suggesting that decreased IGF-1 may contribute to the development of NAFLD-related sarcopenia (106).…”

Time-Dependent Changes in Muscle IGF1-IGFBP5-PAPP System after Sciatic Denervation

“…Hambretch et al (2005) [ 8 ] observed that exercise increases muscle IGF-1, whereas they did not find changes in other tissues. Moreover, it has been demonstrated that muscle IGF-1 deletion induces muscle weakness and atrophy [ 9 ].…”