ArticleThe Journal of clinical investigation2021
Melanocortin 4 receptor signals at the neuronal primary cilium to control food intake and body weight.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Ciliopathies are responsible for short stature and insulin resistance: A systematic review of this clinical association regarding SOFT syndrome.Reviews in endocrine & metabolic disorders · 2024Pooled it
- Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period.The lancet. Diabetes & endocrinology · 2022Trial
- Article
- Primary cilium as a sensory organelle and metabolic hub in health and diseases.Journal of biomedical science · 2026Review
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome.International journal of molecular sciences · 2026Article
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Primary cilia dysfunction: A critical driver of metabolic diseases (Review).International journal of molecular medicine · 2026Review
- In situ proteomics unveils specialized domains for extrasynaptic signaling on neuronal cilia.Science advances · 2026Article
- Smoothened and ciliary GPCRs regulate ciliary protein kinase A activity involved in Hedgehog signal transduction.PLoS biology · 2026Article
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- Exploring the Genetic Overlap Between Metabolic Traits and Anorexia Nervosa.Biological psychiatry global open science · 2026Article
- GPR88 localization to primary cilia in neurons is cell-type specific.Life science alliance · 2026Article
- A Novel Cell-Cell Communication Structure: Tanycyte and Cilia Hypothalamic Unifying Glia-cilia Structure (HUGS).microPublication biology · 2026Article
- In Vivo Gastric Expression of FTO and MC4R in Sleeve Gastrectomy Patients: Diagnostic Utility Without Predictive Value for Weight Loss.Obesity surgery · 2026Article
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- Primary cilia function as hubs for signal transduction.Cell & bioscience · 2025Review
- Effects of Rare Coding Variants in Severe Early-Onset Obesity Genes in the Population-Based UK Biobank Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Tackling ciliary specialization to understand phenotypic variability in human primary ciliopathies.Journal of cell science · 2025Review
- IMPROVE 2023: The 2nd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2025Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Here, using mouse genetic approaches, we found that cilia were required specifically on MC4R-expressing neurons for the control of energy homeostasis. Moreover, these cilia were critical for pharmacological activators of the MC4R to exert an anorexigenic effect. The MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus of the hypothalamus (PVN) were essential to restrict food intake. MC4R activation increased adenylyl cyclase (AC) activity. As with the removal of cilia, inhibition of AC activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, the MC4R signaled via PVN neuron cilia to control food intake and body weight. We propose that defects in ciliary localization of the MC4R cause obesity in human inherited obesity syndromes and ciliopathies.
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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.