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

Abstract

The cafeteria diet contributes to the development of obesity and metabolic syndrome, reduces insulin sensitivity and glucose tolerance. Hepatic hormone fibroblast growth factor 21 (FGF21) promotes adaptation to the consumption of sweet and fatty foods. Female mice are less sensitive to the damaging effects of the cafeteria diet than males, which may be due to the effect of estradiol on the activity of the FGF21 system: on the hepatic expression of the Fgf21 gene, on the blood level of hormone, or on the levels of receptors and coreceptors beta-klotho, which determine the sensitivity of tissues to FGF21. The purpose of this work was to verify this assumption. The effect of estradiol (10 µg/animal once every three days) was evaluated in ovariectomized female C57BL/6 mice who consumed a cafeteria diet (standard food, lard and cookies) for two weeks. Indicators of carbohydrate-fat metabolism, taste preferences, and activity of the FGF21 system were determined. Ovariectomy increased body weight and subcutaneous adipose tissue weight, fat intake, Pomc expression in the hypothalamus, decreased expression of estradiol receptors in the liver and cookie consumption. Estradiol did not have a significant effect on these parameters. In ovariectomized females with estradiol deficiency, blood cholesterol levels and liver expression of the glucose-6-phosphatase gene were lower than in sham operated females, and estradiol normalized these parameters. Ovariectomy lowered, and the administration of estradiol increased the level of coreceptor beta-klotho (Klb) mRNA in the liver and in the hypothalamus. These results suggest that at the initial stages of consumption of sweet and fatty foods, estradiol increases the sensitivity of the liver and hypothalamus to FGF21 and thereby enhances the contribution of the FGF21 system to the processes of adaptation to the cafeteria diet.