Effects and mechanisms of up-regulation of heme oxygenase-1 on uric acid-induced adipocyte dysfunction / 中华老年医学杂志

ABSTRACT

Objective To investigate the effects and mechanisms of up-regulation of heme oxygenase-1(HO-1)on uric acid-induced adipocyte dysfunction. Methods Human bone marrow-derived mesenchymal stem cells(MSCs)were cultured in vitro and second or third generation MSCs were selected and recultured in an adipogenic induction medium,with the addition of various amounts of fructose and uric acid to find the optimal concentrations.Then,the HO-1 inducer cobalt protoporphyrin (CoPP)and the HO-1 inhibitor tin porphyrin(SnMP)were added successively.There were five independent samples in each group.Adipogenesis in MSC-derived adipocytes and droplets were measured by spectrophotometry,expression levels of xanthine oxidase(XO)and NADPH were measured by Western blott,superoxide levels were measured by Luminous spectrometer,and levels of adipogenic markers and HO-1 were measured by reverse transcription-polymerase chain reaction(RT-PCR). Results Fructose at 500 μmol/L and uric acid at 50 mg/L were the optimal concentrations for stimulating adipogenesis in MSC-derived adipocytes(P< 0.05).Compared with the controls,fructose significantly increased the levels of XO expression and uric acid(P< 0.05),and concurrent treatment with fructose and CoPP effectively reversed both XO and uric acid levels to those of the controls(all P<0.05).However,SnMP negated the beneficial effects of CoPP(P< 0.05).Additionally,uric acid decreased the number of small droplets and increased expression levels of adipogenic markers and NADPH(all P<0.05),but proadipogenic mediator levels were reduced with the addition of CoPP(all P<0.05).Furthermore,uric acid reduced expression levels of Wnt 10b,but had no significant effect on HO-1 expression,andthese effects were reversed upon the addition of CoPP(all P<0.05). Conclusions Upregulation of HO-1 can reduce the levels of XO and uric acid,adipogenesis in MSC-derived adipocytes,and also the expression of adipogenic markers and NADPH.Therefore,it plays a role in antioxidant stress.HO-1 agonists may be targets for treating organ damage and controlling weight in elderly obese patients with metabolic syndrome.