Amelioration of Diet-induced Metabolic Abnormalities in Ovariectomized Female Rats Using Estrogen Supplement or Isoflavone Supplement.

Abstract

As women begin to enter menopause, the risks of developing cardiovascular diseases and type 2 diabetes appears to climb. This cluster of risk factors, including obesity, insulin resistance, dyslipidemia, hypertension and decreasing of high density lipoprotein-cholesterol, were called metabolic syndrome. Although there were reports about adverse effects, hormone replacement therapy (HRT) was used to relief menopausal symptoms and treat post-menopausal osteoporosis clinically. Besides estrogen supplement, some healthy food like soy isoflavone, has high affinity to estrogen receptor and it has been reported to improve lipid profiles in post-menopausal women. However, the beneficial effects of HRT and isoflavone on menopausal-associated metabolic syndrome have not been fully verified yet. In our study, we have established a screening platform to evaluate the protective effects of estrogen and isoflavone on developing menopause-associated metabolic syndrome in women. First, we established an animal model of menopause-associated metabolic syndrome. Female rats were ovariectomized to create a menopause status, and then fed with high-fructose diet to induce development of metabolic syndrome. Body weight, adiposity, insulin sensitivity, plasma lipid profiles, and blood pressure were measured. Second, we investigated the protecting effects of hormone replacement therapy on menopause-associated metabolic syndrome in this model. Finally, we evaluated the protecting effects isoflavone on menopause-associated metabolic syndrome in this model. Our results showed that high-fructose feeding induced obesity, insulin resistance, hyperlipidemia, and hypertension in ovariectomized rats. Treatment with estrogen (17£-estradiol, 0.5 mg/pellet, 60-day release) reduced body weight and fat mass and improved insulin sensitivity. Besides, oral administration of soy isoflavone extract (450 mg/day) lowered body weigh, fat mass, improved insulin sensitivity and plasma lipid profiles in high-fructose fed ovariectomized rats. Our results demonstrated that estrogen supplement improved metabolic parameters in ovariectomized rats. Isoflavone also had the similar protective effects, and there was no adverse effect such as hypertriglyceridemia, which presence in rats received estrogen supplement. In conclusion, HRT and isoflavone have significant protective effects on prevention of menopausal-associated metabolic syndrome. This research is supported by DOH098-TD-F-113-098004, Department of Health, Taiwan. (poster)