ArticleCell metabolism2012
Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance.
Article in Cell metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers, 1 of them a synthesis that pooled it.
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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
206 citing papers in PubMed, 1 synthesis or guideline pooled it, 343 citations in OpenAlex.
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- Peripheral selectivity of the novel cannabinoid receptor antagonist TM38837 in healthy subjects.British journal of clinical pharmacology · 2013Trial
- Targeting Cannabinoid 1 Receptor in Macrophages Alleviates Psoriatic Skin Inflammation Through the AUF1-NLRP3 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond energy balance: 2-arachidonoylglycerol at the crossroads of obesity, inflammation, and metabolic dysfunction.Molecular biology reports · 2026Review
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- Endothelial cannabinoid CB1 receptor deficiency reduces shear stress-induced arterial inflammation and lipid uptake.Nature communications · 2026Article
- Tissue-specific roles of monoacylglycerol (MAG) in metabolic diseases.Immunometabolism (Cobham, Surrey) · 2026Review
- Short Communication: The Peripheral Cannabinoid CBInternational journal of molecular sciences · 2026Article
- Progressive endocannabinoid system dysregulation in autosomal dominant polycystic kidney disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Identification of the cannabinoid receptor 1 antagonist, ibipinabant, as a potent inhibitor ofAntimicrobial agents and chemotherapy · 2026Article
- A Novel Approach for the Synthesis of Peripherally Acting Dual Target Inhibitor of Cannabinoid-1 (CB1 Receptor) and Inducible Nitric Oxide Synthase (iNOS) (Molecules (Basel, Switzerland) · 2026Article
- Chronic simultaneous inducible nitric oxide synthase (iNOS) and peripheral cannabinoid CBFrontiers in pharmacology · 2026Article
- Cannabis produces acute hyperphagia in humans and rodents via increased reward valuation for, and motivation to, acquire food.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Endocannabinoid System in the Development and Treatment of Obesity: Searching for New Ideas.International journal of molecular sciences · 2025Review
- Hepatic CB1 receptor signaling triggers GMetabolism: clinical and experimental · 2025Article
- Diet-dependent modulation of energy balance by CB1 signaling in peripheral sensory neurons.iScience · 2025Article
- Targeting cannabinoid receptor 1 for antagonism in pro-fibrotic alveolar macrophages mitigates pulmonary fibrosis.JCI insight · 2025Article
- Metabolic consequences of altered kidney glucose reabsorption under normoglycemic conditions.Molecular metabolism · 2025Article
- Synthesis and Pharmacological Characterization of Novel Peripheral Cannabinoid-1 Receptor Blockers Based on a Tricyclic Scaffold.Journal of medicinal chemistry · 2025Article
- Maladaptive Peripheral Ketogenesis in Schwann Cells Mediated by CBAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
146 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Obesity-related leptin resistance manifests in loss of leptin's ability to reduce appetite and increase energy expenditure. Obesity is also associated with increased activity of the endocannabinoid system, and CB(1) receptor (CB(1)R) inverse agonists reduce body weight and the associated metabolic complications, although adverse neuropsychiatric effects halted their therapeutic development. Here we show that in mice with diet-induced obesity (DIO), the peripherally restricted CB(1)R inverse agonist JD5037 is equieffective with its brain-penetrant parent compound in reducing appetite, body weight, hepatic steatosis, and insulin resistance, even though it does not occupy central CB(1)R or induce related behaviors. Appetite and weight reduction by JD5037 are mediated by resensitizing DIO mice to endogenous leptin through reversing the hyperleptinemia by decreasing leptin expression and secretion by adipocytes and increasing leptin clearance via the kidney. Thus, inverse agonism at peripheral CB(1)R not only improves cardiometabolic risk in obesity but has antiobesity effects by reversing leptin resistance.
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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.