Neuronal Suppressor of Cytokine Signaling 3: Role in Modulating Chronic Metabolic and Cardiovascular Effects of Leptin
Open accessAbstract
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 (V O 2 ) 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 mg/dL), consumed less food (3.0±0.4 versus 3.6±0.2 g/d), and had similar V O 2 (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.
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Neuronal SOCS3 deficiency reduced body weight and food intake, amplified the effects of leptin on blood pressure, and attenuated the adverse metabolic effects of a high-fat, high-fructose diet in mice.
“In addition, neuronal SOCS3 deficiency reduced body weight and food intake, amplified the effects of leptin on BP and attenuated the adverse metabolic effects of a high-fat, high-fructose diet in mice151.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [151]
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- [15]do Carmo JM da Silva AA Wang Z Freeman NJ Alsheik AJ Adi A Hall JE Regulation of blood pressure, appetite, and glucose by leptin after inactivation of insulin receptor substrate 2 signaling in the entire brain or in proopiomelanocortin neurons Hypertension 2015 PMC4763950 26628674
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Obesity, kidney dysfunction and hypertension: mechanistic links
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- Authors
- do Carmo, J. M., da Silva, A. A., Freeman, J. N., Wang, Z., Moak, S. P., Hankins, M. W., Drummond, H. A., & Hall, J. E.
- Affiliations
- 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.)
- University of Mississippi Medical Center (US)
- Venue
- Hypertension
- Published
- 2018-06
- Volume
- 71
- Issue
- 6
- Pages
- 1248-1257
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC5945310
- OpenAlex
- W2803048764
- Cited by
- 11
- References
- 29
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 3 · 2020: 1 · 2019: 4 · 2018: 1
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL‐51971, P01HL051971, GM104357)
- National Institute of General Medical Sciences (GM104357, HL51971, GM115428, P20GM104357, P20GM121334, U54GM115428)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- SOCS3, leptin signaling, leptin, dietary intake, energy expenditure, blood pressure, heart rate, high-fat high-fructose diet, obesity, plasma glucose, hepatic steatosis, body weight, sex differences
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Animals, Blood Pressure, Body Weight, Disease Models, Animal, Female, Male, Neurons, Oxygen Consumption, Signal Transduction, Leptin, Metabolic Syndrome, Mice
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