Agnuside Reduces Visceral Adipocyte Size, Improves Insulin Sensitivity and Reverses Hepatic Steatosis in Ovariectomized Rats

This study aimed to investigate the effects of agnuside (AGN), a phytoestrogen in Vitex agnus-castus, on cellular and metabolic alterations induced by ovariectomy in rats. Ovariectomized (OVX) Wistar rats were used as an animal model of postmenopausal metabolic syndrome. The visceral and subcutaneous adipocyte sizes, the peripheral insulin sensitivity and the occurrence of nonalcoholic fatty liver disease (NAFLD) and liver oxidative damage were evaluated. The results were compared with those obtained from control rats (sham-operated) and OVX rats treated daily with AGN. Obese OVX rats exhibited visceral adipocyte hypertrophy and developed glucose intolerance, hyperinsulinemia, NAFLD and dyslipidemia. AGN exerted beneficial effects on several metabolic parameters in OVX rats, including the improvement in glucose intolerance, hyperinsulinemia and NAFLD. Besides, AGN promoted a general improvement in the liver redox state. Although the reduction of the mesenteric adipocyte size is very likely to be an important mode of action of AGN, some actions of AGN could also involve the interaction with estrogen receptors.