Estradiol Prevents Fat Accumulation and Overcomes Leptin Resistance in Female High-Fat Diet Mice

In premenopausal and menopausal women in particular, suboptimal estrogens have been linked to the development of the metabolic syndrome as major contributors to fat accumulation. At the same time, estrogens have been described to have a role in regulating body metabolic status. We evaluated how endogenous or administered estrogens impact on the changes associated with high-fat diet (HFD) consumption in 2 different paradigms; ovarian-intact and in ovariectomized mice. When estradiol (E2) was cyclically administered to ovarian-intact HFD-fed mice for 12 weeks, animals gained significantly less weight than ovarian-intact vehicle controls (P < .01). This difference was mainly due to a reduced caloric intake but not to an increase in energy expenditure or locomotor activity. This E2 treatment regime to mice exposed to HFD was overall able to avoid the increase of visceral fat content to levels of those found in mice fed a regular chow diet. In the ovariectomized model, the main body weight and fat content redu...