ArticleThe Journal of clinical investigation2014
Ventromedial hypothalamus-specific Ptpn1 deletion exacerbates diet-induced obesity in female mice.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Chemogenetic Excitation of Ventromedial Hypothalamic Steroidogenic Factor 1 (SF1) Neurons Increases Muscle Thermogenesis in Mice.Biomolecules · 2024Article
- Hypoglycemic Effects and Quality Marker Screening ofMolecules (Basel, Switzerland) · 2024Article
- Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.Science advances · 2022Article
- Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism.Science advances · 2022Article
- New Insights of SF1 Neurons in Hypothalamic Regulation of Obesity and Diabetes.International journal of molecular sciences · 2021Review
- FABP4 and MMP9 levels identified as predictive factors for poor prognosis in patients with nonalcoholic fatty liver using data mining approaches and gene expression analysis.Scientific reports · 2019Article
- Role of PTP1B in POMC neurons during chronic high-fat diet: sex differences in regulation of liver lipids and glucose tolerance.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Endocannabinoid Signaling at Hypothalamic Steroidogenic Factor-1/Proopiomelanocortin Synapses Is Sex- and Diet-Sensitive.Frontiers in molecular neuroscience · 2018Article
- Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.Cell metabolism · 2017Article
- Astrocytic Process Plasticity and IKKβ/NF-κB in Central Control of Blood Glucose, Blood Pressure, and Body Weight.Cell metabolism · 2017Article
- Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients.Scientific reports · 2017Article
- Hepatic and serum lipid signatures specific to nonalcoholic steatohepatitis in murine models.Scientific reports · 2016Article
- Knockout of inositol-requiring enzyme 1α in pro-opiomelanocortin neurons decreases fat mass via increasing energy expenditure.Open biology · 2016Article
- Leptin and insulin engage specific PI3K subunits in hypothalamic SF1 neurons.Molecular metabolism · 2016Article
- Article
- Sex-dependent changes in metabolism and behavior, as well as reduced anxiety after eliminating ventromedial hypothalamus excitatory output.Molecular metabolism · 2015Article
- Protein Tyrosine Phosphatases in Hypothalamic Insulin and Leptin Signaling.Trends in pharmacological sciences · 2015Review
- The role of hypothalamic mTORC1 signaling in insulin regulation of food intake, body weight, and sympathetic nerve activity in male mice.Endocrinology · 2015Article
- Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Protein-tyrosine phosphatase 1B (PTP1B) regulates food intake (FI) and energy expenditure (EE) by inhibiting leptin signaling in the hypothalamus. In peripheral tissues, PTP1B regulates insulin signaling, but its effects on CNS insulin action are largely unknown. Mice harboring a whole-brain deletion of the gene encoding PTP1B (Ptpn1) are lean, leptin-hypersensitive, and resistant to high fat diet-induced (HFD-induced) obesity. Arcuate proopiomelanocortin (POMC) neuron-specific deletion of Ptpn1 causes a similar, but much milder, phenotype, suggesting that PTP1B also acts in other neurons to regulate metabolism. Steroidogenic factor-1-expressing (SF-1-expressing) neurons in the ventromedial hypothalamus (VMH) play an important role in regulating body weight, FI, and EE. Surprisingly, Ptpn1 deletion in SF-1 neurons caused an age-dependent increase in adiposity in HFD-fed female mice. Although leptin sensitivity was increased and FI was reduced in these mice, they had impaired sympathetic output and decreased EE. Immunohistochemical analysis showed enhanced leptin and insulin signaling in VMH neurons from mice lacking PTP1B in SF-1 neurons. Thus, in the VMH, leptin negatively regulates FI, promoting weight loss, whereas insulin suppresses EE, leading to weight gain. Our results establish a novel role for PTP1B in regulating insulin action in the VMH and suggest that increased insulin responsiveness in SF-1 neurons can overcome leptin hypersensitivity and enhance adiposity.
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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.