Protein Tyrosine Phosphatase 1B, a Major Regulator of Leptin-Mediated Control of Cardiovascular Function
Open accessAbstract
Background— Obesity causes hypertension and sympathoactivation, a process proposed to be mediated by leptin. Protein tyrosine phosphatase 1B (PTP1B), a major new pharmaceutical target in the treatment of obesity and type II diabetes mellitus, constrains the metabolic actions of leptin, but the extent to which PTP1B regulates its cardiovascular effects is unclear. This study examined the hypothesis that PTP1B is a negative regulator of the cardiovascular effects of leptin. Methods and Results— PTP1B knockout mice had lower body fat but higher mean arterial pressure (116±5 versus 105±5 mm Hg, P <0.05) than controls. Leptin infusion produced a greater anorexic effect in PTP1B knockout mice and a marked increase in mean arterial pressure (135±5 mm Hg) in PTP1B knockout mice only. The decrease in mean arterial pressure in response to ganglionic blockade was higher in PTP1B knockout mice (−38±3% versus −29±3%, P <0.05), which suggests increased sympathetic tone. PTP1B deletion blunted mean arterial pressure responses to phenylephrine injection (55±10% versus 93±7%, P <0.05). Phenylephrine-induced aortic contraction was reduced in PTP1B knockout mice (57.7±9% versus 96.3±12% of KCl, P <0.05), consistent with desensitization to chronically elevated sympathetic tone. Furthermore, PTP1B deletion significantly reduced gene expression of 3 α 1 -adrenergic receptor subtypes, consistent with blunted constriction to phenylephrine. Conclusions— These data indicate that PTP1B is a key regulator of the cardiovascular effects of leptin and that reduced vascular adrenergic reactivity provides a compensatory limit to the effects of leptin on mean arterial pressure.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Protein tyrosine phosphatase 1B dephosphorylates JAK2 and is an important regulator of leptin receptor signalling.
“An important regulator of LepR signalling is protein tyrosine phosphatase IB (PTP1B), which dephosphorylates JAK2 (FIG. 5b).”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [148]
PTP1B deficiency increases blood pressure via sympathetic nervous system stimulation even when leptin concentrations are not elevated, indicating that this pathway influences sympathetic nerve activity and blood pressure through mechanisms other than leptin signalling.
“The observation that PTP1B deficiency increases BP via SNS stimulation, even when leptin concentrations are not elevated148, indicates that this pathway influences SNA and BP through mechanisms other than leptin signalling.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [148]
Genetic disruption of PTP1B signalling enhances leptin signalling and attenuates diet-induced obesity but amplifies the effects of leptin on blood pressure.
“Genetic disruption of PTP1B signalling enhances leptin signalling and attenuates diet-induced obesity but amplifies the effects of leptin on BP148.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [148]
Genetic deletion of PTP1B enhances leptin sensitivity and protects against obesity but exacerbates leptin's BP effects.
“Genetic deletion of PTP1B enhances leptin sensitivity and protects against obesity but exacerbates leptin’s BP effects89.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [89]
The chronic hypertensive effect of leptin in lean rodents is modest, and some investigators have reported no changes in BP during leptin infusions.
“The chronic hypertensive effect of leptin in lean rodents is modest and some investigators have reported no changes in BP during leptin infusions89.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [89]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 40 · Cited by 67
- Authors
- Belin de Chantemèle, E. J., Muta, K., Mintz, J., Tremblay, M. L., Marrero, M. B., Fulton, D. J., & Stepp, D. W.
- Affiliations
- From the Vascular Biology Center (E.J.B.d.C., K.M., J.M., M.B.M., D.J.F., D.W.S.) and Department of Physiology (D.W.S.), Medical College of Georgia, Augusta, Ga; and Goodman Cancer Center and Department of Biochemistry (M.L.T.), McGill University, Montreal, Quebec, Canada.
- McGill University (CA)
- Venue
- Circulation
- Published
- 2009-09
- Volume
- 120
- Issue
- 9
- Pages
- 753-763
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2736363
- OpenAlex
- W2105817828
- Cited by
- 67
- References
- 40
- Citations by year
- 2026: 1 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 5 · 2012: 3
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- Eli Lilly and Company
- National Institutes of Health (5r01hl076533-04)
- National Heart, Lung, and Blood Institute (R01-HL-076533, R01HL092446, R01 HL067533)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- PTP1B, leptin, cardiovascular function, hypertension, sympathetic tone, obesity, phenylephrine vasoconstriction, alpha1-adrenoceptors, anorexia
- MeSH terms
- Adrenergic alpha-Antagonists, Animals, Aorta, Blood Pressure, Hypertension, Male, Mice, Inbred BALB C, Obesity, Phenotype, Phenylephrine, Prazosin, Stress, Physiological, Sympathetic Nervous System, Vasoconstriction, Vasoconstrictor Agents, Receptors, Adrenergic, alpha-1, Mice, Knockout, Leptin, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
