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

ABSTRACT: The increasing prevalence of metabolic-associated fatty liver disease (MAFLD) represents a significant public health challenge, largely attributed to the excessive consumption of sugars and lipids in modern society. 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. Clinical data further indicated a positive correlation between circulating OCY-EV/miR-483-5p levels and MAFLD severity. These findings uncover a novel "bone-liver axis" that regulates hepatic lipid homeostasis and provide promising therapeutic targets for the prevention and treatment of MAFLD, as well as broader implications for metabolic syndrome and related diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE289033 | GEO | 2026/07/01

REPOSITORIES: GEO

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