Role of Proopiomelanocortin Neuron Stat3 in Regulating Arterial Pressure and Mediating the Chronic Effects of Leptin
Although signal transducer and activator of transcription 3 (Stat3) is a key second messenger by which leptin regulates appetite and body weight, its role in specific neuronal populations in metabolic regulation and in mediating the chronic effects of leptin on blood pressure is unknown. The current study tested the hypothesis that Stat3 signaling in proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on mean arterial pressure (MAP), as well as on glucose regulation, energy expenditure, and food intake. Stat3flox/flox mice were crossed with POMC-Cre mice to generate mice with Stat3 deletion specifically in POMC neurons (Stat3flox/flox/POMC-Cre). Oxygen consumption (Vo2), carbon dioxide respiration (Vco2), motor activity, heat production, food intake, and MAP were measured 24 hours/d. After baseline measurements, leptin was infused (4 μg/kg per min, IP) for 7 days. Stat3flox/flox/POMC-Cre mice were hyperphagic, heavier, and had increased respiratory quotients compared with control Stat3flox/flox mice. Baseline MAP was not different between the groups, and chronic leptin infusion reduced food intake similarly in both groups (27 versus 29%). Vo2, Vco2, and heat production responses to leptin were not significantly different in control and Stat3flox/flox/POMC-Cre mice. However, leptin-mediated increases in MAP were completely abolished, and blood pressure responses to acute air–jet stress were attenuated in male Stat3flox/flox/POMC-Cre mice. These results indicate that Stat3 signaling in POMC neurons is essential for leptin-mediated increases in MAP, but not for anorexic or thermogenic effects of leptin.
- Received August 13, 2012.
- Revision received December 11, 2012.
- Accepted January 21, 2013.
- © 2013 American Heart Association, Inc.