# Bovine Milk Extracellular Vesicles Modulate Alveolar Bone Microarchitecture and Mitigate Hepatic Steatosis in Obese Mice Fed a High‐Fat Diet

## TL;DR

Bovine milk extracellular vesicles reduce alveolar bone loss and liver fat in obese mice on a high-fat diet, but do not reverse overall bone or metabolic issues.

## Contribution

This study is the first to explore bovine milk extracellular vesicles' effects on bone and liver in diet-induced obesity.

## Key findings

- MEVs reduced alveolar bone loss and improved osteoblast-osteocyte balance in obese mice.
- MEVs reduced hepatic fat accumulation without altering systemic metabolism or adiposity.
- HF diet caused bone loss in femur and maxilla, metabolic changes, and fatty liver in mice.

## Abstract

Obesity is linked to low‐grade inflammation and systemic bone loss. Current treatments are limited, necessitating new therapeutic approaches. Bovine milk extracellular vesicles (MEVs) modulate bone cell activity, although their role in bone during diet‐induced obesity is unexplored. We evaluated MEV influence on metabolism and bone in a model of high‐fat (HF) diet‐induced obesity. C57BL/6 mice were fed with a control (C) or an obesogenic diet for 12 weeks, with MEV treatment in drinking water starting in the 9th week. HF diet‐fed mice showed loss in the alveolar bone and femur, characterized by a reduced number of osteoblasts, osteocytes, and an increase in osteoclasts. Augmented adiposity and liver fat deposition were found, correlating with hyperglycemia and hyperlipidemia. MEV treatment improved alveolar bone parameters along with a positive balance between osteocytes and osteoblasts versus osteoclast populations. MEVs did not change femur parameters, but reduced osteoclasts. MEVs did not modify systemic metabolism or adipose tissue morphology, but they reduced hepatic fat accumulation. HF diet induces bone loss and metabolic changes. MEV treatment exerts a local cellular effect on alveolar bone, but cannot reverse HF‐induced bone loss in the femur. Nevertheless, MEVs demonstrate benefits in reducing liver fat accumulation.

Obesity induced by an HF diet led to increased adiposity, bone loss in the femur and maxilla, metabolic changes, and fatty liver in mice. Treatment with MEVs did not alter adiposity, metabolic changes, or femoral bone loss, but reduced alveolar bone loss and fat deposition in the liver of obese mice. Created in BioRender. Ferreira, A. (2025) https://BioRender.com/k3zhm7i.