Combined treatment of isoflavone supplementation and exercise restores the changes in hepatic protein expression in ovariectomized rats - a proteomics approach

BACKGROUND Postmenopausal women experience adverse physiological changes caused by estrogen deprivation. Here, we hypothesized that the administration of isoflavone, a phytoestrogn, and/or physical exercise could reverse changes in the levels of hepatic enzymes disturbed by loss of estrogen to ameliorate postmenopause-related health problems. METHODS Thirty-week-old female Sprague-Dawley rats were divided into five groups: a sham-operated (SHAM) group, ovariectomized groups on a regular diet with exercise (EXE) and without exercise (OVX), and ovariectomized groups on an isoflavone supplemented diet with (ISO + EXE) and without exercise (ISO). Proteomic tools were employed to identify candidate hepatic proteins that were differentially expressed among the five animal groups. RESULTS INMT was detected in the SHAM but not in all of the ovariectomized rats. Seven proteins (PPIA, AKR1C3, ALDH2, PSME2, BUCS1, OTC, and GAMT) were identified to have differential expression among the groups. When compared to the SHAM group, the ovariectomy elevated the levels of PPIA, BUCS1, PSME2, AKR1C3, and GAMT while decreasing ALDH2 and OTC. Among these OVX-induced changes, OVX-increased BUCS1 and GAMT levels were noticeably decreased by ISO or EXE and further greatly down-regulated by ISO + EXE. In the case of PSME2, ISO and EXE further increased OVX-upregulated expression levels but ISO + EXE greatly reduced OVX-increased levels. On the other hand OVX-lowered OTC levels were elevated by ISO, EXE, or ISO + EXE. The protein levels of ALDH2, PPIA, and AKR1C3 were not significantly reverted by ISO, EXE or ISO + EXE. CONCLUSION The combination of an isoflavone diet and exercise partly reversed ovariectomy-induced changes in hepatic protein expression levels. Our data suggest that the combinatory regimen of isoflavone supplementation and exercise may be beneficial to menopausal women through modulating hepatic protein expression profiles.