Knockdown of Acid-sensing Ion Channel 1a in the PVN Promotes Metabolic Disturbances in Male Mice

Abstract

Increasing incidence of metabolic disturbances has become a severe public healthcare problem. Ion channels and receptors in the paraventricular nucleus (PVN) of the hypothalamus serve vital roles in modulating neuronal activities and endocrine functions, which are linked to the regulation of energy balance and glucose metabolism. In this study, we found that acid-sensing ion channel 1a (ASIC1a), a Ca2+-permeable cationic ion channel was localized in the PVN. Knockdown of ASIC1a in this region led to significant body weight gain, glucose intolerance, and insulin resistance. Pharmacological inhibition of ASIC1a resulted in an increase in food intake and a decrease in energy expenditure. Our findings suggest ASIC1a in the PVN as a potential new target for the therapeutic intervention of metabolic disorders.

Keywords: acid-sensing ion channel; hypothalamus; insulin resistance; obesity.