ArticleThe Journal of clinical investigation2010
PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 209 citations in OpenAlex.
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Dysregulated glucose metabolism in the visual cortex of human subjects with mild cognitive impairment and Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- Central leptin pathways in metabolic homeostasis.Clinical science (London, England : 1979) · 2025Review
- Molecular mechanisms and neural mediators of leptin action.Genes & development · 2025Review
- Adipose Tissue-Derived Adipokines in Vascular Physiology and Pathophysiology: Insights and Implications.Comprehensive Physiology · 2025Review
- Effects of Combination Treatment with Leptin and Liraglutide on Glucose Metabolism in Insulin-Dependent Diabetic Mice.International journal of molecular sciences · 2025Article
- Regulation of BAT thermogenesis via TRPA1-expressing hypothalamic POMC neurons.Animal cells and systems · 2025Article
- CREB coactivator CRTC1 in melanocortin-4 receptor-expressing cells regulate dietary fat intake.FASEB bioAdvances · 2024Article
- A brown fat-enriched adipokine, ASRA, is a leptin receptor antagonist that stimulates appetite.bioRxiv : the preprint server for biology · 2024Article
- The Mechanism of Leptin Resistance in Obesity and Therapeutic Perspective.Advances in experimental medicine and biology · 2024Review
- Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics.Frontiers in cardiovascular medicine · 2024Review
- Association between PTPN1 polymorphisms and obesity-related phenotypes in European adolescents: influence of physical activity.Pediatric research · 2023Article
- Implications of Hypothalamic Neural Stem Cells on Aging and Obesity-Associated Cardiovascular Diseases.Cells · 2023Review
- Modulatory Effect of Gut Microbiota on the Gut-Brain, Gut-Bone Axes, and the Impact of Cannabinoids.Metabolites · 2022Review
- Adipokines: Deciphering the cardiovascular signature of adipose tissue.Biochemical pharmacology · 2022Review
- MANF in POMC Neurons Promotes Brown Adipose Tissue Thermogenesis and Protects Against Diet-Induced Obesity.Diabetes · 2022Article
- Ser/Thr phosphatases: One of the key regulators of insulin signaling.Reviews in endocrine & metabolic disorders · 2022Review
- Protein Tyrosine Phosphatase 1B Deficiency Improves Glucose Homeostasis in Type 1 Diabetes Treated With Leptin.Diabetes · 2022Article
- The Tyrosine Phosphatase SHP2: A New Target for Insulin Resistance?Biomedicines · 2022Review
- The Effects of Persimmon (Nutrients · 2022Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Protein tyrosine phosphatase 1B (PTP1B) and SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) have been shown in mice to regulate metabolism via the central nervous system, but the specific neurons mediating these effects are unknown. Here, we have shown that proopiomelanocortin (POMC) neuron-specific deficiency in PTP1B or SHP2 in mice results in reciprocal effects on weight gain, adiposity, and energy balance induced by high-fat diet. Mice with POMC neuron-specific deletion of the gene encoding PTP1B (referred to herein as POMC-Ptp1b-/- mice) had reduced adiposity, improved leptin sensitivity, and increased energy expenditure compared with wild-type mice, whereas mice with POMC neuron-specific deletion of the gene encoding SHP2 (referred to herein as POMC-Shp2-/- mice) had elevated adiposity, decreased leptin sensitivity, and reduced energy expenditure. POMC-Ptp1b-/- mice showed substantially improved glucose homeostasis on a high-fat diet, and hyperinsulinemic-euglycemic clamp studies revealed that insulin sensitivity in these mice was improved on a standard chow diet in the absence of any weight difference. In contrast, POMC-Shp2-/- mice displayed impaired glucose tolerance only secondary to their increased weight gain. Interestingly, hypothalamic Pomc mRNA and alpha-melanocyte-stimulating hormone (alphaMSH) peptide levels were markedly reduced in POMC-Shp2-/- mice. These studies implicate PTP1B and SHP2 as important components of POMC neuron regulation of energy balance and point to what we believe to be a novel role for SHP2 in the normal function of the melanocortin system.
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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.