Lifestyle modifications, such as diet and exercise, are becoming increasingly recognized as important strategies to reduce the cardiometabolic risks during menopausal transition because the concern about safety issues in the use of hormone therapy. The present study aimed to investigate the effect and interaction of a combination supplement of Pueraria Lobata/Rehmannia Glutinosa (PR) and aerobic exercise on insulin resistance and metabolic inflexibility observed in an estrogen-deprived animal model. Ovariectomized (OVX) Sprague-Dawley rats fed with a high-fat diet (HFD) were randomly assigned to receive placebo, PR (400 mg/kg body weight), or estradiol (0.2 mg/kg body weight) by oral gavage with or without aerobic exercise for 8 weeks. Indices related to insulin resistance and cardiometabolism were determined in the blood, adipose tissue and muscle. Furthermore, 1H-NMR metabolites were measured in urine. The PR supplementation significantly improved insulin responsiveness in adipose tissue and muscle, leading to a restoration of metabolic flexibility. Adipose tissue became smaller, had more GLUT4 protein in membrane, less macrophage infiltration and higher hormone-sensitive lipase mRNA expression. The metabolic profiles before and after PR supplementation and aerobic exercise were separated based on multivariant analyses of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). Thirty-six metabolites from variable importance plots were screened before and after PR supplementation and aerobic exercise. The 23 metabolites had significantly increased the levels of choline and taurine but significantly decreased levels of ethylene glycol, fumarate and phenylalanine after PR supplementation. Taken together, the results suggest that PR supplement with aerobic exercise has a potential to relieve insulin resistance and its related metabolic defects in postmenopausal women, reflecting changes in metabolite composition.
Acknowledgements: This work was supported by the Bio-Synergy Research Project (NRF-2012M3A9C4048761) of the Ministry of Science, ICT and Future Planning through the National Research Foundation