Role of Suppressor of Cytokine Signaling 3 (SOCS3) in POMC Neurons in Metabolic and Cardiovascular Regulation during Chronic Leptin Infusion

Abstract

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of leptin signaling and is expressed in proopiomelanocortin (POMC) neurons. We previously showed that activation of leptin receptors in POMC neurons mediates the chronic effects of leptin on blood pressure (BP). In this study, we examined whether deletion of SOCS3 specifically in POMC neurons amplifies the chronic metabolic and cardiovascular responses to leptin. 28‐week old male (n=5) and female (n=7) SOCS3flox/flox‐POMC/cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox male (n=5) and female (n=7) mice were implanted with BP telemetry probes. After recovery, 24‐hr mean arterial pressure (MAP), heart rate (HR), body weight, and daily food intake were recorded for 5 consecutive days at baseline. Then leptin was infused (2 mg/kg/day, i.p) via osmotic minipumps for 14 days followed by 6‐days of recovery.Compared to SOCS3flox/flox controls, SOCS3flox/flox‐POMC/cre mice had similar body weight (36.5 ± 2.4 vs 38.5 ± 5.0 g in males and 24.7 ± 0.7 vs 25.2 ± 0.8 g in females) during baseline and consumed similar amounts of food (3.2 ± 0.3 vs 3.3 ± 0.4 g/day in males and 2.6 ± 0.2 vs 2.7 ± 0.1 g/day in females). MAP and HR were similar in SOCS3flox/flox‐POMC/cre and control mice in males (111 ± 5 vs 113 ± 2 mmHg; 546 ± 24 vs 543 ± 26 bpm) and females (105 ± 3 vs 106 ± 2 mmHg; 562 ± 20 vs 573 ± 25 bpm). Leptin infusion reduced body weight by 7–8% in male and female SOCS3flox/flox‐POMC/cre and control mice. Reductions of food intake were similar in SOCS3flox/flox‐POMC/cre and control mice in males (2.5 ± 0.4 vs 2.5 ± 0.7 g/day) and females (2.3 ± 0.3 vs 2.2 ± 0.4 g/day) when calculated as average daily food intake during 10 days of leptin infusion. Leptin infusion transiently increased MAP in male and female SOCS3flox/flox‐POMC/cre and control mice despite decreasing body weight and food intake. Increases of MAP and HR during leptin infusion were similar in male and female SOCS3flox/flox‐POMC/cre mice compared to control mice. Chronic leptin infusion produced similar reductions in fasting blood glucose concentration in SOCS3flox/flox‐POMC/cre and control mice.These results provide no evidence that SOCS3 deletion specifically in POMC neurons amplified the chronic effects of leptin to reduce food intake, body weight, and fasting glucose concentration in male or female mice. Deletion of SOCS3 in POMC neurons also did not substantially amplify the chronic effects of leptin on MAP and HR.Support or Funding InformationFunded by NHLBI PO1HL51971, NIGMS P20GM104357This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.