The Role of Kiss1 Neurons in Regulating Metabolism and Energy Balance.

Hypothalamic kisspeptin, encoded by the Kiss1 gene, serves as an important regulator of the reproductive axis and sexual maturation. Since reproductive physiology is tightly coupled to metabolic cues, metabolic status exerts significant influence on puberty and fertility. Emerging evidence identifies kisspeptin signaling as a key determinant of central energy homeostasis. This review focuses on distinct Kiss1 neuronal populations in the arcuate nucleus of hypothalamus (Arc) and anteroventral periventricular/periventricular nucleus (AVPV/PeN) in regulating energy balance. Arc Kiss1 neurons suppress appetite via activation of POMC neurons and inhibition of AgRP/NPY neurons, while enhance energy expenditure through excitatory projections to the PVN and DMH. In contrast, AVPV/PeN Kiss1 neurons primarily exert inhibitory GABAergic regulation on PVN and DMH neurons. This indicates their suppressive modulatory function, which generally opposes the excitatory metabolic effects mediated by Arc Kiss1 neurons. Peripheral metabolic hormones, including leptin, adiponectin, insulin, and ghrelin, dynamically modulate Kiss1 neuronal activity through direct receptor or indirect POMC/AgRP pathways. By integrating these peripheral signals, Kiss1 neurons act as important modulators of metabolic homeostasis. Taken together, these findings indicate that Kiss1 neuronal pathway may be worth additional investigation in the field of metabolic disorders.