Objective: We recently demonstrated that male, but not female mice fed a high fat (HF) diet developed obesity-hypertension. Castration of female mice conferred obesity-hypertension. The hypothesis of this study is estrogen administration reduces obesity-hypertension in intact male and ovariectomized female HF-fed mice.
Methods and Results: Male (8 weeks old) and ovariectomized female (10 weeks old) C57BL/6 mice were fed a HF diet (60% kcal as fat) for 16 weeks. Exogenous estrogen (36g/ml 17-estradiol) or vehicle (sesame oil) were continuously delivered via silastic tubes implanted subcutaneously in HF-fed male mice from the beginning of HF feeding. For females, HF diet and estrogen administration began 2 weeks after ovariectomy. There was no effect of estrogen administration on the development of obesity in male mice. However, female mice administered estrogen showed a marked reduction in the development of obesity (Body weight: Vehicle: 48.7 ± 1.7 g; Estrogen: 38.9 ± 1.9 g; p<0.05). Administration of estrogen to male HF-fed mice improved glucose tolerance (AUC; estrogen: 42150 ± 1865; Vehicle: 48463 ± 1899; p =0.025). Systolic blood pressure (SBP) was not influenced by estrogen administration in male mice (SBP: Vehicle: 147 ± 4 mmHg; Estrogen: 147 ± 3 mmHg). However, estrogen decreased SBP in female HF-fed ovariectomized mice (SBP: Vehicle: 153 ± 11 mmHg; Estrogen: 137 ± 5 mmHg; p=0.019).
Conclusion: Administration of estrogen to male obese mice had no effect on blood pressure, but improved glucose homeostasis. In ovariectomized HF-fed females, estrogen administration reduced blood pressure. These results suggest that resistance to obesity-hypertension in females may be estrogen-mediated.