Figure 5: The muscle-fat-bone axis. It is been ascertained that a local network exists between the adipose and the bone tissue, which creates what has been defined as the fat-bone axis. In this paracrine circuit, fat influences bone both positively and negatively by secreting Leptin [11] and Adiponectin [12], respectively. Recently, it has been emphasized the function of brown adipocytes which also affect bone tissue byproducing factors that may be secreted to circulation or act directly in the bone marrow environment to induce osteoblast differentiation and osteocyte support for bone formation and bone turnover. Two of these factors, insulin-like growth factor binding protein 2 (IGFBP2) and wingless related MMTV integration site 10b (WNT10b), gather considerable interest because they regulate both bone remodelling and energy metabolism [13]. Moreover, beside its classical functions, bone acts in turn as endocrine organ secreting Osteocalcin, a hormone active on glucose and fat metabolism, stimulating insulin secretion and -cell proliferation [14]. Of further significance, the discovering of Irisin, which is released from muscle, acts as endocrine molecule targeting adipose tissue by increasing energy expenditure [3] and bone by enhancing osteoblast differentiation. As shown in this work, Irisin is a new protagonist of the axis, which now could be considered as the muscle-fat-bone axis.