Mechanical overload induces muscle hypertrophy in mice with lowered serum IGF-1

Access full-text files




Zannikos, Symeon Vasilios

Journal Title

Journal ISSN

Volume Title



Decreased serum levels of IGF-1 result in lower muscle and body weights. Muscular autocrine/paracrine IGF-I may be stimulated in response to mechanical overload. Purpose: to determine whether normal levels of serum IGF-I are required for the increased muscle mass tha occurs in habitual mechanical overload. Design: The Liver IGF-I Deficient (LID) mouse has selective disruption of the liver IGF-I alleles, resulting in 20-25% of normal serum IGF-1 levels. Wildtype, LL, mice have normal circulating levels of IGF-1. LID and LL mice, 15-16 mos of age, were divided into resistance trained (LID-TR n=11, LL-TR n = 10) and sedentary groups (LID-NT n = 9, LL-NT n = 8). The resistance training protocol consisted of ladder climbing (85°, 1.5cm spacing), utilizing progressive overload. Initially weights, 50% of body weight (BW) were attached to the base of their tail, and the resistance was progressively increased. The training protocol was performed twice a day, every third day for 16-18 weeks, with the mice pulling over 3X their body weight during their last bouts. The in situ physiological parameters of the Plantaris muscle were determined. Results: SP[subscript o],SP[subscript t], as well as TPT & 1/2 RT were the same among groups. The Plantaris muscle was the most responsive to the weight training, exhibiting a 12 % (p < 0.05) increase in absolute weight in both training groups vs. their sedentary counterparts. Other hindlimb muscles increased by 7-9% (p <0.05). Hematoxylin-Eosin staining revealed cellular damage in both training groups. The LID-TR group sustained damage in 1.4% of myofibers, while the LL-TR only showed damage in 0.5% of myofibers (p <0.05). No cellular damage was evident in either sedentary group. Central nuclei were visualized utilizing laminin antibody staining. In the LID-TR group 1.8% of myofibers showed central nuclei vs. 0.5% in the LL-TR (p <0.05). The central nuclei were mostly localized around the areas of cellular damage. Conclusion: The degree of hypertrophy was the greatest in the plantaris and FHL muscle, as expected from this type of training. In this experiment, decreased serum IGF-1Ea levels did not attenuate the muscular hypertrophy induced by habitual mechanical overload. The LID-TR group was able to hypertrophy to the same degree as the LL-TR animals. Even though they weighed significantly less than their sedentary counterparts, their muscle weights in the FHL and Plantaris were greater. Satellite activation was not hindered either as evidenced by the significantly higher levels of central nuclei in the LID-TR group. The increased number of central nuclei found in the LID-TR group is likely due in part to the increased levels of damage, as the majority was localized around the areas of damage. Neverthless, the data shows that satellite activation is not hindered in the presence of reduced IGF-1Ea. The compensatory mechanisms for the adaptation evidenced in this study need to be elucidated. Release of IGF-1Eb can be a likely reason, as IGF-1Eb has been shown to be more potent in inducing muscle hypertrophy, and thus may be able to compensate for the reduced serum levels of IGF-1Ea (Goldspink 2002). Individual steps among the cascade of intracellular signals activated by IGF-1Ea may also be amplified to allow normal hypertrophy during muscle overload


LCSH Subject Headings