Role of IGF-II in follistatin-induced skeletal muscle hypertrophy. S. Kalista, H. Gilson, O. Schakman, P. Lause, N. Decroly and J.P. Thissen. “5th Cachexia conference”, Barcolona, Spain, December 2009.

Kalista, S Schakman, Olivier [UCL] Lause, P Decroly, N Thissen, Jean-Paul [UCL]

Follistatin (FS) exerts its muscle anabolic action by inhibiting several members of the TGF-β superfamily, including Myostatin. We have previously shown that FS-induced muscle hypertrophy is associated with increased levels of Insulin-like Growth Factor (IGF)-II mRNA, a potent inducer of myogenesis. The aim of this study was to investigate the role of IGF-II in FS-induced muscle hypertrophy. To test this hypothesis, FS was overexpressed in muscle of IGF-II KO mice. The tibialis anterior (TA) muscles of KO IGF-II as well as wild type (WT) mice were electroporated with the plasmid pM1-FS288 (left leg) and the control plasmid pM1 (right leg). 17 days after electroporation, TA muscles were removed, weighted and frozen for biochemical analysis or embedded in paraffin for morphological analysis. Our results show that FS overexpression in TA muscle of WT mice caused muscle hypertrophy characterized by increased muscle mass (+36%, 50.2 ± 2.9 vs 37.1 ± 1.3 mg, P<0.01; n=5), fiber cross sectional area (CSA) (2.3-fold, 4081 ± 225 vs 1812 ± 114 μm², P<0.001; n=5) and IGF-II mRNA (2.3-fold, p<0.05; n=5). In IGF-II KO mice, FS induced the same degree of muscle hypertrophy. Indeed, muscle mass was increased by 33% (23.1 ± 1.6 vs 17.4 ± 1.0, P<0.05; n=6) and CSA by 2-fold (3973 ± 387 vs 1970 ± 113, P<0.01; n=6). In conclusion, our data suggest that IGF-II is not mandatory for muscle hypertrophy induced by FS. So, IGF-II must be considered as a marker more than a crucial player in FS-induced muscle hypertrophy.