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
Yasmin Silva Forte,
Vany Nascimento-Silva,
Caio Andrade-Santos,
Isadora Ramos-Andrade,
Georgia Correa Atella,
Luiz Guilherme Kraemer-Aguiar,
Paulo Roberto Falcão Leal,
Mariana Renovato-Martins,
Christina Barja-Fidalgo
Affiliations
Yasmin Silva Forte
Laboratory of Cellular & Molecular Pharmacology, Department of Cell Biology, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Vany Nascimento-Silva
Laboratory of Cellular & Molecular Pharmacology, Department of Cell Biology, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Caio Andrade-Santos
Laboratory of Cellular & Molecular Pharmacology, Department of Cell Biology, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Isadora Ramos-Andrade
Laboratory of Cellular & Molecular Pharmacology, Department of Cell Biology, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Georgia Correa Atella
Institute of Medical Biochemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Luiz Guilherme Kraemer-Aguiar
Obesity Unit, Multiuser Clinical Research Center (CePEM), Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Paulo Roberto Falcão Leal
Obesity Unit, Multiuser Clinical Research Center (CePEM), Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Mariana Renovato-Martins
Department of Molecular & Cellular Biology, Universidade Federal Fluminense, Rio de Janeiro 24020-141, Brazil
Christina Barja-Fidalgo
Laboratory of Cellular & Molecular Pharmacology, Department of Cell Biology, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
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.
