Neuronal Suppressor of Cytokine Signaling 3 Role in Modulating Chronic Metabolic and Cardiovascular Effects of Leptin

作者：do Carmo Jussara M.^*; da Silva Alexandre A.; Freeman John Nathan; Wang Zhen; Moak Sydney P.; Hankins Michael W.; Drummond Heather A.; Hall John E.

来源：Hypertension, 2018, 71(6): 1248-1257.

DOI：10.1161/HYPEKTENSIONAHA.118.11127

• appetite
• blood pressure
• heart rate
• hypertension
• obesity

We determined whether deficiency of neuronal SOCS3 (suppressor of cytokine signaling 3) a potential negative regulator of leptin signaling amplifies the chronic effects of leptin on food intake, energy expenditure, glucose, and blood pressure (BP) and protects against adverse cardiometabolic effects of obesity. BP and heart rate were recorded by telemetry, and oxygen consumption (VO2) was monitored in 22-week-old mice with nervous system SOCS3 deficiency (SOCS3-Nestin-Cre) and control mice (SOCS3(flox/flox)) fed normal or high-fat high-fructose diet from 6 to 22 weeks of age. Compared with controls, SOCS3-Nestin-Cre mice had lower plasma glucose (124 +/- 7 versus 146 +/- 10 mgldL), consumed less food (3.0 +/- 0.4 versus 3.6 +/- 0.2 g/d), and had similar VO2 (77 +/- 6 versus 73 3 mL/kg per minute) and BP (103 3 versus 107 +/- 3 mm Hg) but higher heart rate (666 +/- 15 versus 602 +/- 17 bpm). In mice fed the normal diet, leptin infusion for 7 days caused similar reductions in food intake (2.3 +/- 0.1 versus 2.4 +/- 0.2 g) but greater increases in BP (15 +/- 3 versus 7 2 mm Hg) in SOCS3-Nestin-Cre compared with controls. Leptin reduced blood glucose concentrations in both groups. Male or female SOCS3-Nestin-Cre fed high-fat high-fructose diet exhibited less weight gain, body fat, and liver steatosis and greater energy expenditure and heart rate compared with controls. Female SOCS3-Nestin-Cre mice fed high-fat high-fructose diet had higher BP compared with controls. Thus, neuronal SOCS3 seems to play an important role in cardiometabolic regulation because neuronal SOCS3 deficiency reduced body weight and food intake while amplifying leptin's effects on appetite and BP and attenuating the adverse metabolic effects of high-fat high-fructose diet.

• 出版日期2018-6