Estudio de la influencia de la osteopontina en el desarrollo de la obesidad y sus comorbilidades

Resumen

In a first study we analysed the effect of the lack of osteopontin (OPN) on the development of obesity and hepatic steatosis induced by a high-fat diet (HFD) using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT) and liver in wild type (WT) mice under a HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue extracellular matrix remodelling and reduced adipocyte size than WT mice under a HFD. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. OPN deficiency prevented hepatic steatosis. Furthermore, OPN-KO mice exhibited higher body temperature and improved brown adipose tissue (BAT) function. In a second study we analyzed the effect of sleeve gastrectomy (SG) on circulating levels of OPN and its expression in adipose tissue and liver in HFD-induced obese rats. Circulating OPN levels decreased with HFD feeding remaining unaltered after SG. The expression of Spp1 in EWAT and liver was not modified by SG. The global improvement of metabolism after SG appears not to involve changes in serum OPN concentrations as well as in EWAT and liver expression in rats. In a third study we compared the effect of Roux-en-Y gastric bypass (RYGB) and SG on plasma levels of OPN in humans. RYGB increased circulating OPN levels, while they remained unaltered after SG. The increase in OPN levels after RYGB could be related to the increased bone resorption in relation to its well-known effects on bone of this malabsorptive procedure in comparison to the merely restrictive SG. Therefore, our results suggest that OPN could be an attractive target for the treatment of obesity and associated pathologies.