EFFECTS OF NEONATAL ESTRADIOL TREATMENT ON REGULATING SEXUAL DIFFERENTIATION OF DAILY RHYTHMS UNDERLYING DIET-INDUCED OBESITY IN FEMALE MICE

Sex differences of the brain and behavior often require the combination of organizational and activational effects of sex hormones. The activational effects of estrogens in adult female mice protect daily eating and activity rhythms from disruption by high-fat diet feeding and inhibit diet-induced obesity. However, male mice have disrupted eating rhythms when fed high-fat diet and this causes obesity. Treatment of adult male mice with estradiol does not protect rhythms from disruption by high-fat diet, as it does in females. In this study, we sought to determine whether the organizational effects of estradiol masculinize the daily eating and activity rhythms underlying diet-induced obesity in female mice. We injected female mice with estradiol daily for the first five days after birth. As adults, these female mice were ovariectomized and implanted with tubing containing either estradiol or oil. We found that adult treatment of female mice with estradiol inhibited diet-induced obesity. Adult, but not neonatal, estradiol treatment increased activity but had no effect on food consumption. Interestingly, adult and not neonatal estradiol treatment restored high-amplitude activity rhythms in ovariectomized female mice fed high-fat diet. Together, these results demonstrate that neonatal estrogen treatment does not masculinize daily rhythms that regulate diet-induced obesity.