Osteopontin-deficient progenitor cells display enhanced differentiation to adipocytes

ObjectiveOsteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation.MethodsOPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1^−/− female mice. Gene expression for hypoxia, inflammation and adipogenesis was checked in WT vs. Spp1^−/− mice (n = 15). Adipocytes progenitor cells (APC) were isolated by fluorescence cell sorting and role of OPN deficiency in adipogenesis was investigated by cell images and RT-PCR.ResultsWe show that Spp1^−/− maintained normal body and fat-pad weights, although hypoxia and inflammation markers were significantly reduced. In contrast, expression of genes involved in adipogenesis was increased in WAT from Spp1^−/− mice. Strikingly, APC from Spp1^−/− were diminished but differentiated more efficiently to adipocytes than those from control mice.ConclusionsAPC from SC-WAT of lean OPN-deficient mice display an enhanced capacity for differentiating to adipocytes. These alterations may explain the healthy expansion of WAT in the OPN-deficient model which is associated with reduced inflammation and insulin resistance.