Osteokines in Nonalcoholic Fatty Liver Disease

To critically summarize evidence on the potential role of osteokines in the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD).

There are emerging data supporting that certain osteokines, which are specific bone-derived proteins, may beneficially or adversely affect hepatic metabolism, and their alterations in the setting of osteoporosis or other bone metabolic diseases may possibly contribute to the development and progression of NAFLD. There is evidence showing a potential bidirectional association between NAFLD and bone metabolism, which may imply the existence of a liver-bone axis. In this regard, osteocalcin, osteoprotegerin, bone morphogenic protein 4 (BMP4) and BMP6 appear to have a positive impact on the liver, thus possibly alleviating NAFLD, whereas osteopontin, receptor activator of nuclear factor kappa Β ligand (RANKL), sclerostin, periostin, BMP8B, and fibroblast growth factor 23 (FGF23) appear to have a negative impact on the liver, thus possibly exacerbating NAFLD. The potential implication of osteokines in NAFLD warrants further animal and clinical research in the field that may possibly result in novel therapeutic targets for NAFLD in the future.