ArticleThe Journal of clinical investigation2007
The central melanocortin system directly controls peripheral lipid metabolism.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.
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.
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Who cites it
210 citing papers in PubMed, 388 citations in OpenAlex.
- Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program.Obesity (Silver Spring, Md.) · 2013Trial
- Nos1 neurons in the paraventricular hypothalamic area modulate lipid metabolism via the sympathetic nervous system in male mice.Nature communications · 2026Article
- Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement.Biomolecules · 2026Review
- Hypothalamic regulation of energy homeostasis: Quo vadis.Reviews in endocrine & metabolic disorders · 2026Review
- Beyond satiety: unraveling the complex roles of POMC neurons in behavior and metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Transcriptome and plasma proteome analyses identify susceptibility genes and proteins for alcohol-related hepatocellular carcinoma.Human genomics · 2026Article
- Adipose Tissue and Central Nervous System Crosstalk: Roles in Pain and Cognitive Dysfunction.Biomedicines · 2025Review
- Low cholesterol levels and cardiovascular risk in obesity due to MC4R deficiency.Nature medicine · 2025Article
- Maternal monosaccharide diets modulate melanocortin-4 receptor signaling and metabolic state in rat offspring.Pharmacological reports : PR · 2025Article
- Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk.Nature medicine · 2025Article
- An Enlarging Mass Superimposed on a Giant Congenital Melanocytic Nevus: A Case Report and Review of Literature.Clinical case reports · 2025Article
- Rapid modulation of gut microbiota composition by hypothalamic circuits in mice.Nature metabolism · 2025Article
- CPT1C deficiency in SF1 neurons impairs early metabolic adaptation to dietary fats, leading to obesity.Molecular metabolism · 2025Article
- Integrative Strategies for Preventing and Managing Metabolic Syndrome: The Impact of Exercise and Diet on Oxidative Stress Reduction-A Review.Life (Basel, Switzerland) · 2025Review
- Glucagon-like Peptide-2 Acts Partially Through Central GLP-2R and MC4R in Mobilizing Stored Lipids from the Intestine.Nutrients · 2025Article
- Hypothalamic neural circuits regulating energy expenditure.Vitamins and hormones · 2025Review
- Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.Cellular and molecular life sciences : CMLS · 2024Article
- Cardiometabolic Risk Markers in Children With Obesity and Variants inJournal of the Endocrine Society · 2024Article
- A Healthy Dietary Pattern May Have a Protective Effect Against Cardiovascular Disease Through Its Interaction With the MC4R Gene Polymorphism.Clinical nutrition research · 2024Review
- A human obesity-associated MC4R mutation with defective Gq/11α signaling leads to hyperphagia in mice.The Journal of clinical investigation · 2024Article
150 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 6 institutions in 4 countries.
Funding
Abstract
Disruptions of the melanocortin signaling system have been linked to obesity. We investigated a possible role of the central nervous melanocortin system (CNS-Mcr) in the control of adiposity through effects on nutrient partitioning and cellular lipid metabolism independent of nutrient intake. We report that pharmacological inhibition of melanocortin receptors (Mcr) in rats and genetic disruption of Mc4r in mice directly and potently promoted lipid uptake, triglyceride synthesis, and fat accumulation in white adipose tissue (WAT), while increased CNS-Mcr signaling triggered lipid mobilization. These effects were independent of food intake and preceded changes in adiposity. In addition, decreased CNS-Mcr signaling promoted increased insulin sensitivity and glucose uptake in WAT while decreasing glucose utilization in muscle and brown adipose tissue. Such CNS control of peripheral nutrient partitioning depended on sympathetic nervous system function and was enhanced by synergistic effects on liver triglyceride synthesis. Our findings offer an explanation for enhanced adiposity resulting from decreased melanocortin signaling, even in the absence of hyperphagia, and are consistent with feeding-independent changes in substrate utilization as reflected by respiratory quotient, which is increased with chronic Mcr blockade in rodents and in humans with loss-of-function mutations in MC4R. We also reveal molecular underpinnings for direct control of the CNS-Mcr over lipid metabolism. These results suggest ways to design more efficient pharmacological methods for controlling adiposity.
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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.