A reduction of food intake – and concurrent loss of body weight – in combination with physical hyperactivity are main symptoms of the eating disorder anorexia nervosa. Continuous loss of fat mass results in hypoleptinemia, which initiates multiple starvation-related adaptive functions. Although leptin administration showed beneficial effects in treatment of symptoms of anorexia nervosa, including anxiety, neuronal mechanisms of possible anxiety-relieving action of leptin are not known.Here, combining calcium imaging and opto- or chemogenetics in freely behaving mice, we investigated functions of leptin-expressing neurons in the lateral hypothalamus (LepRLH), the brain region crucial for the regulation of feeding. We found that this cell population signals anxiogenic stimuli, and activation of LepRLH cells reduces anxiety-related behaviors in multiple behavioral arrays. To mimic anorexia nervosa symptoms in mice, we used a well-established activity-based anorexia (ABA) model. Mice undergoing the protocol of time-restricted feeding and free access to running wheels displayed a reliable increase of running wheel activity despite continuous loss of body weight. Using calcium imaging, we found that LepRLH cells responded to running in a wheel. Additionally, chemogenetic activation of LepRLH neurons altered the development of anorexia-like behavior. This study suggests a role of LepRLH neurons in regulation of anxiety-related behaviors in health and in a model of anorexia nervosa.We gratefully acknowledge support by the ERC Consolidator Grant (772994, FeedHypNet, to T.K.) and DFG (233886668-GRK1960, to R.F., Project-ID 431549029 – SFB 1451 to T.K., EXC2030 CECAD to T.K., and EXC 2030 – 390661388, to A.P.).