Bovine Milk Extracellular Vesicles as a Preventive Treatment for Bone Dysfunction and Metabolic Alterations in Obese Mice Fed a High-Refined Carbohydrate Diet.

Obesity may cause bone loss due to changes in energy and bone metabolism. Bone loss treatment is still limited, requiring new therapeutic strategies. Bovine milk extracellular vesicles (MEVs) are nanoparticles that act as modulators of cell signaling. While its benefits have already been demonstrated in bone loss, the underlying mechanisms must be better elucidated. To evaluate the effect of MEVs on bone loss in obesity, BALB/c mice were fed a chow diet or a high-refined carbohydrate (HC) diet for 12 weeks and treated or not with MEVs from the 9th week. Mice fed the HC diet showed bone loss in the maxillary and long bones related to detrimental changes in the bone cell profile. As expected, the HC diet induced hyperglycemia and dyslipidemia, lipid accumulation in adipose and liver, and elevated receptor activator of nuclear factor kappa-Β ligand (RANKL)/osteoprotegerin (OPG) ratio and Pentraxin 3 (PTX3) levels. MEV treatment protected from bone loss, increasing osteoblast and osteocyte numbers and reducing osteoclastic activity. Additionally, MEVs diminished adiposity, liver damage, serum glucose, triglyceride, and PTX3 levels, and the RANKL/OPG ratio. MEVs offer a protective effect against bone loss and improve metabolic outcomes in an HC diet-induced obesity model, suggesting that metabolic improvements may contribute to their bone-protective role.