Blocking a Lipid Messenger from Osteocytes: A Novel Strategy for Prevention and Treatment of Metabolic Associated Fatty Liver Disease

The liver serves as the central regulator of systemic energy homeostasis, while the bones, as high-energy-consuming organs, are now recognized for their active role in metabolic regulation. In this study, osteocyte-derived extracellular vesicles (OCY-EV) are identified as critical mediators in the crosstalk between bone and hepatic lipid metabolism.

OCY-EV are found to facilitate hepatic lipid accumulation through miR-483-5p, which activates lipid metabolism-related pathways, thereby promoting fatty acid uptake and lipogenesis in hepatocytes. Genetic ablation of OCY-EV secretion or antagonism of miR-483-5p markedly attenuated hepatic steatosis in high-fat diet-induced MAFLD models. Moreover, treatment with bone resorption inhibitors, such as denosumab and zoledronic acid, reduced the release of OCY-EV from bone matrix, leading to decreased circulating OCY-EV/miR-483-5p levels and amelioration of MAFLD progression.