Effect of Estradiol on Carbohydrate-Fat Metabolism and FGF21 System Activity in Female C57BL/6 Mice with Short-Term Consumption of the Cafeteria Diet

The cafeteria diet contributes to the development of obesityand metabolic syndrome, reduces insulin sensitivity and glucosetolerance. Hepatic hormone fibroblast growth factor 21 (FGF21) promotes adaptationto the consumption of sweet and fatty foods. Female mice are lesssensitive to the damaging effects of the cafeteria diet than males,which may be due to the effect of estradiol on the activity of the FGF21system: on the hepatic expression of the Fgf21 gene,on the blood level of hormone, or on the levels of receptors andcoreceptors beta-klotho, which determine the sensitivity of tissuesto FGF21. The purpose of this work was to verify this assumption.The effect of estradiol (10 µg/animal once every three days) wasevaluated in ovariectomized female C57BL/6 mice who consumed a cafeteriadiet (standard food, lard and cookies) for two weeks. Indicatorsof carbohydrate-fat metabolism, taste preferences, and activityof the FGF21 system were determined. Ovariectomy increased bodyweight and subcutaneous adipose tissue weight, fat intake, Pomc expression in the hypothalamus,decreased expression of estradiol receptors in the liver and cookieconsumption. Estradiol did not have a significant effect on these parameters.In ovariectomized females with estradiol deficiency, blood cholesterollevels and liver expression of the glucose-6-phosphatase gene werelower than in sham operated females, and estradiol normalized theseparameters. Ovariectomy lowered, and the administration of estradiolincreased the level of coreceptor beta-klotho (Klb)mRNA in the liver and in the hypothalamus. These results suggest thatat the initial stages of consumption of sweet and fatty foods, estradiolincreases the sensitivity of the liver and hypothalamus to FGF21and thereby enhances the contribution of the FGF21 system to the processesof adaptation to the cafeteria diet.