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Contribution of Leptin Signaling to the Sex- and Estrus Cycle-dependent Regulation of Adaptive Behaviors

Deema Awad1, Rebecca Figge-Schlensok1, Tatiana Korotkova1, Anne Petzold1

1 Physiological Institute, University Hospital, Cologne

Leptin, a hormone secreted by adipocytes, is renowned for its crucial role in regulating energy homeostasis, feeding behavior, and metabolism. Nevertheless, emerging evidence suggests that its influence extends beyond metabolic regulation to encompass various behavioral domains, including sociosexual behavior. Using single-cell calcium imaging, we have previously shown that leptin-receptor expressing  neurons of the lateral hypothalamus (LepRLH) of both males and females preferentially respond to conspecifics of the same sex, i.e., potential mates. While leptin treatment in adult male mice reduced food intake, the same treatment increased social exploration. Although leptin levels strongly differ in males and females, little is known about sex-specific differences in leptin signaling. In this study, we performed an extensive pharmacological screen to evaluate the effects of leptin treatment for the expression of essential innate behaviors - feeding behavior, social and sexual behaviors, as well as exploration under anxiogenic conditions – both in males and naturally cycling females. While acute leptin treatment following overnight food deprivation decreased food intake in both males and females in the non-receptive estrus cycle phase, the same treatment  increased food intake in female mice during the receptive phase of the estrus cycle. These findings suggest that leptin signaling may affect the expression of innate behaviors in a sex- and cycle-dependent manner.