Tibolone Reverses NAFLD in Ovariectomised Rats by Reducing Adiposity and Insulin Resistance

This study aimed to investigate the effects of tibolone, a synthetic steroid, on several metabolic dysfunctions induced by oestrogen deficiency, in rats. Ovariectomised (OVX) rats were used as animal model of postmenopausal metabolic syndrome. The OVX rats were treated with daily doses of tibolone (0.16 mg/kg) and the results were compared with control (sham-operated) and OVX untreated rats. Tibolone reduced the adiposity and the visceral adipocyte size in OVX rats. The insulin sensitivity was also improved, and a decrease in the activity of the adipose tissue hormone-sensitive lipase enzyme was recorded. The lower lipolysis by visceral adipocytes, associated with the recovery of peroxisomal -oxidation by tibolone may have contributed to the reversion of NAFLD in treated OVX rats. The reduction of liver lipid contents resulted in a general improvement in the liver redox state. In addition, tibolone reduced the mitochondrial ROS generation and restored the activity of glucose-6-phosphate dehydrogenase. Tibolone also exerted antioxidant effects on inguinal adipose tissue. Tibolone exerted several beneficial effects on cellular and metabolic dysfunctions induced by ovariectomy in rats. One important mode of action of tibolone was the reduction of the visceral adipocyte size, corroborating the relationship between this one and the development and progression of several comorbidities associated with metabolic syndrome.