ArticleNature communications2023
Structural insights into the mechanism of leptin receptor activation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Classification of Congenital Leptin Deficiency.The Journal of clinical endocrinology and metabolism · 2024Pooled it
- Monoallelic pathogenic variants in LEPR do not cause obesity.American journal of human genetics · 2024Trial
- The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026Review
- The perineurium integrates leptin with its sympathetic outflow to protect against obesity.Nature metabolism · 2026Article
- Peptide Hormones in Appetite Regulation: A Complex Network.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.Current obesity reports · 2026Review
- Tetrahedral framework nucleic acids as a promising vehicle for small molecule drugs of traditional Chinese medicine: application to disease prevention and treatment.Journal of nanobiotechnology · 2026Review
- Evaluating the causal role of LEPR signaling in 16 cancers: A drug-target Mendelian randomization study.Medicine · 2026Article
- Modulatory Role of Moringa Oleifera-Loaded Silver Nanoparticles on UCP1 and PPARGC1A Genes Expression in an Obesity Rat Model.Applied biochemistry and biotechnology · 2026Article
- Leptin Receptor b (LEPRb) Mutations Disrupt Hypothalamic Control of the Reproductive Axis.International journal of molecular sciences · 2026Review
- Exploring the Genetic Overlap Between Metabolic Traits and Anorexia Nervosa.Biological psychiatry global open science · 2026Article
- Leptin receptor rs1137101 polymorphism and altered leptin-sOb-R axis contribute to type 2 diabetes risk in Gujarat population.Frontiers in endocrinology · 2026Article
- The leptin fragment Lep116-130 attenuates hedonic consumption and sucrose-seeking in mice.Frontiers in pharmacology · 2026Article
- Tirzepatide Synergizes with Leptin on Weight Loss and Restoring Metabolic Homeostasis in Diet-induced Obesity Model.bioRxiv : the preprint server for biology · 2025Article
- Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Association Between Obesity and Serum Leptin Levels in Brazilian Female Shift Workers.Diseases (Basel, Switzerland) · 2025Article
- Intestinal-related substances in obesity regulation: A comprehensive review.World journal of gastrointestinal pharmacology and therapeutics · 2025Review
- Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells.Oncoimmunology · 2025Article
- Structural and functional characterization of the Pro64Ser leptin mutant: Implications for congenital leptin deficiency.Biophysical journal · 2025Article
- Leptin as a key driver for organ fibrogenesis.Science advances · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Leptin is an adipocyte-derived protein hormone that promotes satiety and energy homeostasis by activating the leptin receptor (LepR)-STAT3 signaling axis in a subset of hypothalamic neurons. Leptin signaling is dysregulated in obesity, however, where appetite remains elevated despite high levels of circulating leptin. To gain insight into the mechanism of leptin receptor activation, here we determine the structure of a stabilized leptin-bound LepR signaling complex using single particle cryo-EM. The structure reveals an asymmetric architecture in which a single leptin induces LepR dimerization via two distinct receptor-binding sites. Analysis of the leptin-LepR binding interfaces reveals the molecular basis for human obesity-associated mutations. Structure-based design of leptin variants that destabilize the asymmetric LepR dimer yield both partial and biased agonists that partially suppress STAT3 activation in the presence of wild-type leptin and decouple activation of STAT3 from LepR negative regulators. Together, these results reveal the structural basis for LepR activation and provide insights into the differential plasticity of signaling pathways downstream of LepR.
Indexed as
Identifiers
What OpenQuestion holds
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.