Soybean-hop alleviates estrogen deficiency-related bone loss and metabolic dysfunction in ovariectomized rats fed a high-fat diet

Soybeans and hops have been traditionally used as a natural estrogen replacement therapy and their major active ingredients, isoflavones and prenylflavanones, are known to have estrogenic/antiestrogenic effects depending on the target organ. However, their potential benefits are still subject to controversies. The present study investigated the dual effect of soy isoflavones plus hop prenylflavanones (Soy-Hop) on bone loss and metabolic dysfunction under estrogen deficient condition. Rats were sham-operated (n = 10) or ovariectomized (OVX; n = 40) and then fed a high-fat diet (HFD) to develop hyperlipidemia in OVX rats within the experimental period of 8 weeks. The OVX/HFD rats were assigned to four groups to receive different doses of Soy-Hop (0, 30, 100, and 300 mg/kg) by oral gavage for 8 weeks. High-dose Soy-Hop significantly suppressed OVX/HFD-induced increases in food intake, body weight gain, fat mass, and circulating levels of leptin, adiponectin, LDL-cholesterol, total cholesterol, triglycerides, glucose, and insulin. High-dose Soy-Hop also attenuated OVX/HFD-induced elevation of osteocalcin, alkaline phosphatase, and CTX in plasma and RANKL/OPG gene expression ratio in femur. These findings were confirmed visually by confocal analysis of GLUT4 translocation in soleus muscle cells and micro-computed tomography scanning of the distal femoral epiphysis, respectively. These results suggest that Soy-Hop may have potential to ameliorate estrogen deficiency-related alterations in both metabolism and bone quality, at least in part, by hormonal factors secreted by adipocytes.