Protective effect of equol on bone in postmenopausal rats with nonalcoholic fatty liver disease

Objective To observe the osteoprotective effect of equol (Eq) on postmenopausal rats with nonalcoholic fatty liver disease (NAFLD), and to explore its underlying mechanism. Methods Forty-eight 6-week-old female Sprague-Dawley (SD) rats were randomly divided into control group, model group, low-, middle- and high-dose Eq groups [20, 40 and 80 mg/(kg·d)], and estradiol intervention group [E2, 0.25 mg/(kg·d)], with 8 rats in each group. The control group was given sham operation and normal diet. The other groups were given ovariectomy (OVX) combined with high-fat diet. After 16 weeks, the body weight and length of rats were measured, BMI and Lee's index were calculated, and the changes of bone mineral density (BMD) and bone microstructure of rats were detected. After anesthesia, the rats were killed to detect the levels of serum estrogen, TNF-α and IL-6. The liver and femur tissues were observed for morphological changes, and the expression of insulin-like growth factor-1 (IGF-1) in the liver and bone was detected by Western blotting and qRT-PCR. Results In the model group, BMI and Lee's index were increased significantly, the liver tissue was obviously injured, the estrogen level and BMD were obvioiusly decreased, and the bone microstructure was seriously damaged, suggesting that postmenopausal NAFLD was complicated with obvious bone injury. The treatment of Eq or E2 increased the level of serum estrogen and BMD, decreased BMI, Lee's index and serum TNF-α and IL-6 levels, attenuated steatosis and lipid accumulation in bone microstructure, and enhanced the expression of IGF-1 at protein and mRNA level in the liver and bone. Conclusion Eq can improve the bone injury of postmenopausal NAFLD rats and shows a bone protective effect. The mechanism may partially be related to Eq promoting the expression of IGF-1 and reducing inflammation. x