The tolerance of fish to fasting offers a model to study the regulatory mechanisms and changes produced when feeding is restored. Gilthead sea bream juveniles were exposed to a 21-days fasting period followed by 2 h to 7-days refeeding. Fasting provoked a decrease in body weight, somatic indexes, and muscle gene expression of members of the Gh/Igf system, signaling molecules (akt, tor and downstream effectors), proliferation marker pcna, myogenic regulatory factors, myostatin, and proteolytic molecules such as cathepsins or calpains, while most ubiquitin-proteasome system members increased or remained stable. In bone, downregulated expression of Gh/Igf members and osteogenic factors was observed, whereas expression of the osteoclastic marker ctsk was increased. Refeeding recovered the expression of Gh/Igf system, myogenic and osteogenic factors in a sequence similar to that of development. Akt and Tor phosphorylation raised at 2 and 5 h post-refeeding, much faster than its gene expression increased, which occurred at day 7. The expression in bone and muscle of the inhibitor myostatin (mstn2) showed an inverse profile suggesting an inter-organ coordination that needs to be further explored in fish. Overall, this study provides new information on the molecules involved in the musculoskeletal system remodeling during the early stages of refeeding in fish.conditions has been characterized and the ratio of the circulating levels of Gh and Igf1 is considered a good marker of growth quality in terms of its relation with body indexes or muscle fibers composition 12,13 .Muscle growth is also controlled by myogenic regulatory factors (MRFs) (MyoD, Myf5, Myog and Mrf4), and the negative endogenous regulator myostatin, as well as other factors that control sequentially the process of development and growth 6,14,15 . The effects of fasting and refeeding on myogenesis have been studied in diverse fish species 6,10,16 demonstrating the function of the different MRFs during the metabolic arrest caused with food limitation and the subsequent activation when feeding is restored. Furthermore, during fasting and refeeding, proteolytic molecules play a remarkable role to adapt to the changes in amino acids supply. This is more important in fish that have a specific and enhanced protein metabolism. The main endogenous proteolytic systems, each one performing specific degradative or regulatory functions according to the nutritional conditions are, calpains, cathepsins and ubiquitin-proteasome, all of which are well-known in fish, especially salmonids [17][18][19] , but also in gilthead sea bream [20][21][22] .In addition to muscle, bone is also an important tissue for skeletal and locomotion functions, but also, as a reservoir of minerals that is clearly affected when nutrition is restricted. Essential during development, synchronicity between bone and muscle is required for proper musculoskeletal growth 23,24 . Besides to being induced by the Gh/Igf system, the process of osteogenesis is also regulated by skeleton-derived factors that...