Tributyltin induces a transcriptional response without a brite adipocyte signature in adipocyte models.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Tributyltin (TBT), a peroxisome proliferator-activated receptor γ (PPARγ)/retinoid X receptor (RXR) ligand and founding member of the environmental obesogen chemical class, induces adipocyte differentiation and suppresses bone formation. A growing number of environmental PPARγ ligands are being identified. However, the potential for environmental PPARγ ligands to induce adverse metabolic effects has been questioned because PPARγ is a therapeutic target in treatment of type II diabetes. We evaluated the molecular consequences of TBT exposure during bone marrow multipotent mesenchymal stromal cell (BM-MSC) differentiation in comparison to rosiglitazone, a therapeutic PPARγ ligand, and LG100268, a synthetic RXR ligand. Mouse primary BM-MSCs (female, C57BL/6J) undergoing bone differentiation were exposed to maximally efficacious and human relevant concentrations of rosiglitazone (100 nM), LG100268 (100 nM) or TBT (80 nM) for 4 days. Gene expression was assessed using microarrays, and in silico functional annotation was performed using pathway enrichment analysis approaches. Pathways related to osteogenesis were downregulated by all three ligands, while pathways related to adipogenesis were upregulated by rosiglitazone and TBT. However, pathways related to mitochondrial biogenesis and brown-in-white (brite) adipocyte differentiation were more significantly upregulated in rosiglitazo

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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