Abstract
Circulating 178-estradiol (E2) controls energy homeostasis and feeding behaviors primarily by its nuclear re-ceptor, estrogen receptor (ER) alpha. As such, it is important to understand the role of ER alpha signaling in the neuro-endocrine control of feeding. Our previous data indicated that the loss of ER alpha signaling through estrogen response elements (ERE) alters food intake in a female mouse model. Hence, we hypothesize that ERE-dependent ER alpha is necessary for typical feeding behaviors in mice. To test this hypothesis, we examined feeding behaviors on low-fat diet (LFD) and high-fat diet (HFD) in three mouse strains: total ER alpha knockout (KO), ER alpha knockin/ knockout (KIKO), which lack a functional DNA-binding domain, and their wild type (WT) C57 littermates comparing intact males and females and ovariectomized females with or without E2 replacement. All feeding behaviors were recorded using the Biological Data Acquisition monitoring system (Research Diets). In intact male mice, KO and KIKO consumed less than WT mice on LFD and HFD, while in intact female mice, KIKO consumed less than WT and KO. These differences were primarily driven by shorter meal duration in the KO and KIKO. In ovariectomized females, E2-treated WT and KIKO consumed more LFD than KO driven in part by an increase in meal frequency and a decrease in meal size. On HFD, WT consumed more than KO with E2, again due to effects on meal size and frequency. Collectively, these suggest that both ERE-dependent and-independent ER alpha signaling are involved in feeding behaviors in female mice depending on the diet consumed.