Format

Send to

Choose Destination
Hypertension. 2018 Jun;71(6):1248-1257. doi: 10.1161/HYPERTENSIONAHA.118.11127. Epub 2018 Apr 23.

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

Author information

1
From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson (J.M.d.C., A.A.d.S., J.N.F., Z.W., S.P.M., M.W.H., H.A.D., J.E.H.) jdocarmo@umc.edu.
2
From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson (J.M.d.C., A.A.d.S., J.N.F., Z.W., S.P.M., M.W.H., H.A.D., J.E.H.).
3
Faculdade de Medicina, Departamento de Fisiologia, Barão de Mauá University Center, Ribeirão Preto, São Paulo, Brazil (A.A.d.S.).
4
and Faculdade de Medicina, Departamento de Fisiologia, Universidade Estadual de Minas Gerais, Passos, Brazil (A.A.d.S.).

Abstract

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 (SOCS3flox/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 mg/dL), 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.

KEYWORDS:

appetite; blood pressure; heart rate; hypertension; obesity

PMID:
29686012
PMCID:
PMC5945310
[Available on 2019-06-01]
DOI:
10.1161/HYPERTENSIONAHA.118.11127
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center