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Grun et al. Novel murine model for studying human obesity and its complications



DOI:10.1038/bonekey.2016.97

The cytokine osteopontin (OPN) can bind with CD44 and many different integrin receptors and so stimulate pathways that initiate the inflammatory response. In this study, Grun et al. evaluated the humanized SPP1 (hSPP1) mouse model as a tool with which to study diet-induced human insulin resistance and obesity.

When the mice were fed a high fat diet, hSPP1 mice and WT mice became obese and suffered obesity-induced complications such as liver inflammation and reduced insulin sensitivity.

hSPP1 mice and wild-type mice fed a low fat diet were very similar in terms of their body weight, phenotype and behavior until the age of 6 weeks. After that time point, hSPP1 mice gained more weight each week compared with WT controls and became less sensitive to insulin. The hSPP1 mice also showed adipocyte hypertrophy, high OPN expression and had a greater mass of gonadal white adipose tissue (GWAT).

The authors suggest that the hSPP1 mouse model could be used to research new therapeutic strategies to tackle diet-induced inflammation due to OPN overexpression.

Editor’s comment: OPN is well known to bind hydroxyapatite with high affinity. The SPP1 gene is also overexpressed in the kidney. This study attests to the ‘pleiotropic’ function of this protein, and underlines the need to focus on developing strategies to target OPN in a variety of pathologies.


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