# Unlocking the Secrets of Adipose Tissue: How an Obesity-Associated Secretome Promotes Osteoblast Dedifferentiation via TGF-β1 Signaling, Paving the Path to an Adipogenic Phenotype

## TL;DR

Obesity-related fat tissue releases signals that cause bone-building cells to lose their identity and become more fat-like, with TGF-β1 playing a key role.

## Contribution

This study reveals how obesity-associated fat secretions directly cause osteoblast dedifferentiation and promote an adipogenic shift via TGF-β1 signaling.

## Key findings

- Obese adipose secretomes induce osteoblast dedifferentiation and mesenchymal-like changes.
- Exposure to obese secretomes increases adipogenic markers and lipid droplet formation in osteoblasts.
- TGF-β1 is a key mediator in the observed dedifferentiation and adipogenic effects.

## Abstract

Background: Obesity poses a significant global health challenge, given its association with the excessive accumulation of adipose tissue (AT) and various systemic disruptions. Within the adipose microenvironment, expansion and enrichment with immune cells trigger the release of inflammatory mediators and growth factors, which can disrupt tissues, including bones. While obesity’s contribution to bone loss is well established, the direct impact of obese AT on osteoblast maturation remains uncertain. This study aimed to explore the influence of the secretomes from obese and lean AT on osteoblast differentiation and activity. Methods: SAOS-2 cells were exposed to the secretomes obtained by culturing human subcutaneous AT from individuals with obesity (OATS) or lean patients, and their effects on osteoblasts were evaluated. Results: In the presence of the OATS, mature osteoblasts underwent dedifferentiation, showing an increased proliferation accompanied by a morphological shift towards a mesenchymal phenotype, with detrimental effects on osteogenic markers and the calcification capacity. Concurrently, the OATS promoted the expression of mesenchymal and adipogenic markers, inducing the formation of cytoplasmic lipid droplets in SAOS-2 cells exposed to an adipogenic differentiation medium. Additionally, TGF-β1 emerged as a key mediator of these effects, as the OATS was enriched with this growth factor. Conclusions: Our findings demonstrate that obese subcutaneous AT promotes the dedifferentiation of osteoblasts and increases the adipogenic profile in these cells.