HO-1 Upregulation Attenuates Adipocyte Dysfunction,Obesity,and Isoprostane Levels in Mice Fed High Fructose Diets

Background. fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ros. ho-1 is a potent antioxidant gene that plays a key role in decreasing ros and isoprostanes. we examined whether the fructose-mediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction of ho-1 would decrease both isoprostane levels and adipogenesis. methods and results. we examined the effect of fructose,on adipogenesis in human mscs in the presence and absence of copp,an inducer of ho-1. fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (p<0.05). levels of heme and isoprostane in fructose treated msc-derived adipocytes were increased. copp reversed these effects and markedly increased ho-1 and the wnt signaling pathway. the high fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels (p<0.05 versus control). fructose diets decreased ho-1 and adiponectin levels in adipose tissue. induction of ho-1 by copp decreased isoprostane synthesis (p<0.05 versus fructose). conclusion. fructose treatment resulted in increased isoprostane production and adipocyte dysfunction,which was reversed by the increased expression of ho-1. © 2014 zeid khitan et al.