Fos-induced osteosarcoma growth causes a cachexia-like phenotype in mice and correlates with high Fgf21 serum levels.

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)

BACKGROUND: The dimeric AP-1 transcription factor has been described as a regulator of bone metabolism, but also of adipocyte biology. More specifically, its family members adopt specific functions in the regulation of adipocyte differentiation and adipose tissue hypoxia, but also in controlling lipolysis, energy expenditure and insulin sensitivity. METHODS: In this study, we analyzed the role of the AP-1 family member Fos, whose ubiquitous over-expression in transgenic mice has been described to cause osteosarcoma formation, on adipose tissue, glucose and lipid metabolism. More specifically, we analyzed the metabolic phenotype of the respective mouse model by histological analyses, monitoring gene expression, determination of serum parameters and ex vivo adipogenesis assays. RESULTS: We show that FosTg mice additionally display an age-dependent loss of white adipose tissue, which is associated with reduced adipocyte size. Quantitative real-time PCR analyses of white adipose tissue as well as in vitro studies using adipocyte-derived stromal cells excluded a cell-autonomous defect in adipocyte differentiation. However, FosTg mice displayed low circulating glucose levels along with increased glucose tolerance and insulin sensitivity. By proteomic analysis we identified elevated serum levels of fibroblast growth factor 21 (Fgf21) in FosTg mice which could explain the observed redu

Evidence level

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

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