Role of SOCS3 in POMC Neurons in metabolic and cardiovascular regulation.

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of leptin signaling. We previously showed that the chronic effects of leptin on blood pressure (BP) and glucose regulation are mediated by stimulation of pro-opiomelanocortin (POMC) neurons. In this study, we examined the importance of endogenous SOCS3 in POMC neurons in control of metabolic and cardiovascular function and potential sex differences. Male and female SOCS3flox/flox/POMC-Cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox mice were studied during a control diet (CD) or high fat diet (HFD) and during chronic leptin infusion. On CD, male and female SOCS3flox/flox/POMC-Cre mice were lighter in body weight despite similar food intake compared to control mice. Male SOCS3flox/flox/POMC-Cre mice exhibited increased energy expenditure. BP and heart rate were similar in male and female SOCS3flox/flox/POMC-Cre and control mice on CD. On a HFD, male and female SOCS3flox/flox/POMC-Cre mice showed attenuated weight gain. Female SOCS3flox/flox/POMC-Cre mice exhibited greater HFD-induced elevations in baseline BP and BP responses to air jet stress test compared to control mice. Chronic leptin infusion produced similar responses in all groups for food intake, body weight, oxygen consumption, blood glucose, BP and heart rate. Thus, SOCS3 deficiency in POMC neurons influences body weight regulation in CD and HFD and differentially affects BP and energy balance in a sex specific manner, but does not amplify the dietary, glycemic or cardiovascular effects of leptin.