Abstract P076: Suppressor of Cytokine Signaling 3 (SOCS3) in POMC Neurons and Its Role in Regulating Blood Pressure, Body Weight and Glucose in Obesity

Abstract

Suppressor of cytokine signaling 3 (SOCS3), a negative regulator of leptin signaling, may be involved in development of obesity-induced leptin resistance. Although we previously showed that activation of proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on blood pressure (BP), the role of SOCS3 in modulating BP in obesity is still unclear. In this study, we investigated the role of SOCS3 specifically in POMC neurons in regulating body weight, glucose handling and BP in mice fed a normal or high fat (45%, HFD) chow. Male and female SOCS3flox/flox-POMC/cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox mice were used. Food intake and body weight were measured from 8 to 16 weeks of age, and a glucose tolerance test (GTT) was performed at 20 wks of age. At 22 wks of age, mice were implanted with telemetry probe to measure BP and heart rate (HR) and fed a HFD for 6 weeks. Compared to control mice, both male and female SOCS3flox/flox-POMC/cre mice were lighter at 16 wks (29.1 ± 3.5 vs 31.9 ± 3.6 g in male and 21.5 ± 2.2 vs 26.1 ± 5.7 in female, n=9-11, p<0.05) but food intake was similar in both groups. Only male SOCS3flox/flox-POMC/cre mice exhibited improved glucose handling (AUC: 1059 ± 52 vs 1283 ± 54 mg/dL x 120 min, n=7-10, p<0.05 ) and no differences were observed in female mice. When fed normal chow, BP was similar in SOCS3flox/flox-POMC/cre and control mice (116 ± 7 vs 113 ± 5 mmHg) at 23 wks. After a HFD for 6 weeks, SOCS3flox/flox-POMC/cre mice had a greater BP increase compared to control mice (7.2 ± 1.9 vs 0.9 ± 1.8 mmHg, n=4-9, P<0.05) but no significant differences were observed in food intake or body weight between two groups. These results suggest that SOCS3 deletion specifically in POMC neurons reduced body weight in male and female mice, and improved glucose handling only in male mice. HFD increased BP in SOCS3flox/flox-POMC/cre but not in control mice, suggesting that SOCS3 in POMC neurons may modulate BP response to HFD.