ArticleCell metabolism2011
Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance.
Article in Cell metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 101 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
101 citing papers in PubMed, 175 citations in OpenAlex.
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- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Increased leptin signaling drives the response of hypothalamic LepRb neurons to diet-induced obesity.Molecular metabolism · 2026Article
- PTPN1/PTPN2 inhibition improves NK cancer therapy by enhancing IL-2 and mitigating TGFβ1 responses.EMBO reports · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Targeting Protein Tyrosine Phosphatases via PROteolysis-TArgeting Chimeras (PROTACs): Current Developments and Prospects.Molecules (Basel, Switzerland) · 2025Review
- Molecular mechanisms and neural mediators of leptin action.Genes & development · 2025Review
- Lard intake results in better hypothalamic leptin responsiveness than beef tallow intake during overnutrition.PloS one · 2025Article
- Chronic sleep deprivation disturbs energy balance modulated by suprachiasmatic nucleus efferents in mice.BMC biology · 2024Article
- Chemical Epigenetic Regulation Secondary Metabolites Derived fromMolecules (Basel, Switzerland) · 2024Article
- The Mechanism of Leptin Resistance in Obesity and Therapeutic Perspective.Advances in experimental medicine and biology · 2024Review
- Breast feeding, obesity, and asthma association: clinical and molecular views.Clinical and molecular allergy : CMA · 2023Review
- A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity.Nature communications · 2023Article
- Cannabinoid receptor type 1 (CBiScience · 2023Article
- Small Molecule Degraders of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase for Cancer Immunotherapy.Angewandte Chemie (International ed. in English) · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Ultraviolet Radiation Exposure and its Impacts on Cutaneous Phosphorylation Signaling in Carcinogenesis: Focusing on Protein Tyrosine PhosphatasesPhotochemistry and photobiology · 2023Review
- Dual PTP1B/TC-PTP Inhibitors: Biological Evaluation of 3-(Hydroxymethyl)cinnoline-4(International journal of molecular sciences · 2023Article
- The natural product rotundic acid treats both aging and obesity by inhibiting PTP1B.Life medicine · 2022Article
- Leptin signaling and leptin resistance.Medical review (2021) · 2022Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
In obesity, anorectic responses to leptin are diminished, giving rise to the concept of "leptin resistance." Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high-fat-diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.