Paraventricular NUCB2/Nesfatin-1 Supports Oxytocin and Vasopressin Neurons to Control Feeding Behavior and Fluid Balance in Male Mice

Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.