Kisspeptin Neurons in the Arcuate Nucleus of the Hypothalamus Orchestrate Circadian Rhythms and Metabolism

Successful reproduction in female mammals is precisely timed and must be able to withstand the metabolic demand of pregnancy and lactation. We show that kisspeptin-expressing neurons in the arcuate hypothalamus (Kiss1 ^ARH ) of female mice control the daily timing of food intake, along with the circadian regulation of locomotor activity, sleep, and core body temperature. Toxin-induced silencing of Kiss1 ^ARH neurons shifts wakefulness and food consumption to the light phase and induces weight gain. Toxin-silenced mice are less physically active and have attenuated temperature rhythms. Because the rhythm of the master clock in the suprachiasmatic nucleus (SCN) appears to be intact, we hypothesize that Kiss1 ^ARH neurons signal to neurons downstream of the master clock to modulate the output of the SCN. We conclude that, in addition to their well-established role in regulating fertility, Kiss1 ^ARH neurons are a critical component of the hypothalamic circadian oscillator network that times overt rhythms of physiology and behavior. Sex hormones can impact circadian rhythms, but the neural mechanism(s) remains largely unresolved. Padilla et al. demonstrate that sex-hormone-sensitive Kiss1 neurons in the arcuate hypothalamus are a necessary component of circadian rhythms.