Fig. 3. Modulation of skeletal muscle growth by the IGF system in teleost fish. Muscle derived IGFBPs may be controlling IGFs actions in fish muscle. However, it remains to be
determined which IGFBPs are positive or negative modulators of IGFs actions. IGFs stimulate muscle growth in fish by promoting the proliferation of myogenic cells, protein synthesis, and hypertrophy. Whether muscle-derived (mdIGF1) and/or liver-derived IGF1 (ldIGF1) is/are the main promoter of muscle mass accretion in fish is not known,
although current evidence supports both sources of IGF1 as regulators of growth of this tissue. The molecular mechanisms involved in IGFs actions start when these ligands
bind to IGF1R, triggering the activation of the MAPK/ERK and PI3K/AKT/TOR signaling pathways. The biological function and role of M6P/IGF2R is unknown in fish muscle. The
MAPK/ERK pathway stimulates the transcription of igf1, and the PI3K/AKT/TOR activates the transcription of several genes belonging to the IGF system, including igf1. Amino
acids also stimulate the transcription of igf1, probably via TOR. Therefore, two alternative signaling pathways (IGFs/AKT/TOR and amino acids) besides the JAK2/STAT5
stimulate the transcription of igf1. TOR also stimulates the activation of P70S6K and 4EBP1. Moreover, IGFs affect the gene expression of mrfs and components of the MSTN
system. However, the signaling pathways involved in the transcriptional regulation of these genes are not known. Altogether, the regulation mediated by IGFs of all
aforementioned molecules and signaling pathways stimulates protein synthesis and muscle hypertrophy. In parallel, IGF1 inhibits protein degradation and muscle atrophy
via the PI3K/AKT/TOR and by using an alternative pathway, the PI3K/AKT/FOXO. Altogether, these molecules are regulating a balance between protein degradation and synthesis, thus maintaining skeletal muscle mass in teleost fish. This diagram represents a simplified illustration summarizing the components and the effects of the IGF system in fish muscle growth. For further details see Section 5. White-symbols (i.e. molecules and boxes) and question marks (?) represent unstudied molecules or biological processes in fish skeletal muscle. Symbols (i.e. molecules and boxes) colored in blue and green denote positive and negative modulators of fish muscle growth, respectively.