ArticleThe Journal of clinical investigation2010
Disruption of hypothalamic leptin signaling in mice leads to early-onset obesity, but physiological adaptations in mature animals stabilize adiposity levels.
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 74 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
74 citing papers in PubMed, 114 citations in OpenAlex.
- Secretion Patterns of Leptin: A Key Component in the Regulation of Energy Homeostasis and Its Therapeutic Applications.Biomolecules · 2026Review
- Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain.Cell reports · 2026Article
- Glucagon-Like Peptide 1 (GLP-1) Action on Hypothalamic Feeding Circuits.Endocrinology · 2025Review
- Molecular mechanisms and neural mediators of leptin action.Genes & development · 2025Review
- Molecular Imprints of Clinical Comorbidities in Hypothalamic Extracellular Vesicles at the Onset of Obesity.ACS omega · 2025Article
- AgRP neuron hyperactivity drives hyperglycemia in a mouse model of type 2 diabetes.The Journal of clinical investigation · 2025Article
- Neural and hormonal mechanisms of appetite regulation during eating.Frontiers in nutrition · 2025Review
- Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis.Nature communications · 2024Article
- CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.Nature communications · 2023Article
- Suppression of food intake by Glp1r/Lepr-coexpressing neurons prevents obesity in mouse models.The Journal of clinical investigation · 2023Article
- Hindbrain circuits in the control of eating behaviour and energy balance.Nature metabolism · 2022Review
- An orally active plant Rubisco-derived peptide increases neuronal leptin responsiveness.Scientific reports · 2022Article
- Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption.Psychological medicine · 2022Article
- Leptin, the brain and energy homeostasis: From an apparently simple to a highly complex neuronal system.Reviews in endocrine & metabolic disorders · 2022Review
- A nexus of lipid andFrontiers in endocrinology · 2022Review
- Revealing the role of the human blood plasma proteome in obesity using genetic drivers.Nature communications · 2021Article
- FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia.Blood advances · 2020Article
- Identification of the leptin receptor sequences crucial for the STAT3-Independent control of metabolism.Molecular metabolism · 2020Article
- Hypothalamic mTORC2 is essential for metabolic health and longevity.Aging cell · 2019Article
- Leptin's hunger-suppressing effects are mediated by the hypothalamic-pituitary-adrenocortical axis in rodents.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Distinct populations of leptin-sensing neurons in the hypothalamus, midbrain, and brainstem contribute to the regulation of energy homeostasis. To assess the requirement for leptin signaling in the hypothalamus, we crossed mice with a floxed leptin receptor allele (Leprfl) to mice transgenic for Nkx2.1-Cre, which drives Cre expression in the hypothalamus and not in more caudal brain regions, generating LeprNkx2.1KO mice. From weaning, LeprNkx2.1KO mice exhibited phenotypes similar to those observed in mice with global loss of leptin signaling (Leprdb/db mice), including increased weight gain and adiposity, hyperphagia, cold intolerance, and insulin resistance. However, after 8 weeks of age, LeprNkx2.1KO mice maintained stable adiposity levels, whereas the body fat percentage of Leprdb/db animals continued to escalate. The divergence in the adiposity phenotypes of Leprdb/db and LeprNkx2.1KO mice with age was concomitant with increased rates of linear growth and energy expenditure in LeprNkx2.1KO mice. These data suggest that remaining leptin signals in LeprNkx2.1KO mice mediate physiological adaptations that prevent the escalation of the adiposity phenotype in adult mice. The persistence of severe adiposity in LeprNkx2.1KO mice, however, suggests that compensatory actions of circuits regulating growth and energy expenditure are not sufficient to reverse obesity established at an early age.
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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.