ReviewDiabetes, obesity & metabolism2022
Melanocortin-4 receptor complexity in energy homeostasis,obesity and drug development strategies.
Review in Diabetes, obesity & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Impact of Bariatric Surgery on the Expression of Fertility-Related Genes in Obese Women: A Systematic Review ofInternational journal of molecular sciences · 2025Pooled it
- The Genetic Basis of Childhood Obesity: A Systematic Review.Nutrients · 2023Pooled it
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Vigorous Physical Activity Mitigates Susceptibility to Obesity Associated with Risk Genotypes ofEpigenomes · 2026Article
- Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.Current obesity reports · 2026Review
- Multidimensional Predictors of Tirzepatide Efficacy: Clinical, Genetic, and Molecular Biomarkers for Glycemic, Weight, and Organ Protection.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison.International journal of obesity (2005) · 2026Article
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- Modulating food intake by nasal application of peptides targeting melanocortin 4 receptor and ghrelin receptor systems.Brain communications · 2026Article
- Recent Updates on the Role of Genetic and Epigenetic Factors in the Pathogenesis of the Metabolic Syndrome.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Interplay Between Enteroendocrine Hormone (Leptin) and Adipokines (Ghrelin and Adiponectin) with Gastric Expression of FTO and MC4R Genes.Scientific reports · 2025Article
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- Precision medicine for obesity: current evidence and insights for personalization of obesity pharmacotherapy.International journal of obesity (2005) · 2025Review
- Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link.Journal of the National Cancer Center · 2025Review
- Setmelanotide-mediated MC4R activation improves hypothalamic obesity via CaMKK2/AMPK pathways.Frontiers in pharmacology · 2025Article
- G × E interactions as a basis for toxicological uncertainty.Archives of toxicology · 2023Article
- Molecular Analysis and Conformational Dynamics of Human MC4R Disease-Causing Mutations.Molecules (Basel, Switzerland) · 2022Article
- Melanocortin-4 receptor complexity in energy homeostasis,obesity and drug development strategies.Diabetes, obesity & metabolism · 2022Review
- Structural and Functional Diversity of Animal Toxins Interacting With GPCRs.Frontiers in molecular biosciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The melanocortin-4 receptor (MC4R) has been critically investigated for the past two decades, and novel findings regarding MC4R signalling and its potential exploitation in weight loss therapy have lately been emphasized. An association between MC4R and obesity is well established, with disease-causing mutations affecting 1% to 6% of obese patients. More than 200 MC4R variants have been reported, although conflicting results as to their effects have been found in different cohorts. Most notably, some MC4R gain-of-function variants seem to rescue obesity and related complications via specific pathways such as beta-arrestin (ß-arrestin) recruitment. Broadly speaking, however, dysfunctional MC4R dysregulates satiety and induces hyperphagia. The picture at the mechanistic level is complicated as, in addition to the canonical G stimulatory pathway, the ß-arrestin signalling pathway and ions (particularly calcium) seem to interact with MC4R signalling to contribute to or alleviate obesity pathogenesis. Thus, the overall complexity of the MC4R signalling spectra has broadened considerably, indicating there is great potential for the development of new drugs to manage obesity and its related complications. Alpha-melanocyte-stimulating hormone is the major endogenous MC4R agonist, but structure-based ligand discovery studies have identified possible superior and selective agonists that can improve MC4R function. However, some of these agonists characterized in vitro and in vivo confer adverse effects in patients, as demonstrated in clinical trials. In this review, we provide a comprehensive insight into the genetics, function and regulation of MC4R and its contribution to obesity. We also outline new approaches in drug development and emerging drug candidates to treat obesity.
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What Socratic 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 Socratic graph.