ArticleMolecular metabolism2018
Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Classification of Congenital Leptin Deficiency.The Journal of clinical endocrinology and metabolism · 2024Pooled it
- Scalable hypothalamic neuron differentiation from human pluripotent stem cells suitable for modeling metabolic disorders.Stem cell reports · 2026Article
- Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide.Molecular metabolism · 2024Article
- Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2.Cell genomics · 2024Article
- Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model.Science advances · 2024Article
- Integrating a Multi-label Deep Learning Approach with Protein Information to Compare Bioactive Peptides in Brain and Plasma.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Targeting the central melanocortin system for the treatment of metabolic disorders.Nature reviews. Endocrinology · 2023Review
- Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR ofbioRxiv : the preprint server for biology · 2023Article
- Recent advances in mass spectrometry analysis of neuropeptides.Mass spectrometry reviews · 2023Review
- Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant.The Journal of clinical endocrinology and metabolism · 2022Article
- Mass Spectrometry Approaches Empowering Neuropeptide Discovery and Therapeutics.Pharmacological reviews · 2022Review
- The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.Endocrinology · 2022Article
- Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.Endocrinology · 2021Review
- Depletion of Alpha-Melanocyte-Stimulating Hormone Induces Insatiable Appetite and Gains in Energy Reserves and Body Weight in Zebrafish.Biomedicines · 2021Article
- Melanocortin System in Kidney Homeostasis and Disease: Novel Therapeutic Opportunities.Frontiers in physiology · 2021Review
- L-Cell Expression of Melanocortin-4-Receptor Is Marginal in Most of the Small Intestine in Mice and Humans and Direct Stimulation of Small Intestinal Melanocortin-4-Receptors in Mice and Rats Does Not Affect GLP-1 Secretion.Frontiers in endocrinology · 2021Article
- Mass spectrometric characterisation of the circulating peptidome following oral glucose ingestion in control and gastrectomised patients.Rapid communications in mass spectrometry : RCM · 2020Article
- Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R).Physiological research · 2020Review
- Proopiomelanocortin Processing in the Hypothalamus Is Directly Regulated by Saturated Fat: Implications for the Development of Obesity.Neuroendocrinology · 2020Article
- Reduced Stability and pH-Dependent Activity of a Common Obesity-Linked PCSK1 Polymorphism, N221D.Endocrinology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveThe lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated.
methodsWe analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from human pluripotent stem cells (hPSCs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the sequence and quantify the production of hypothalamic neuropeptides, including those derived from POMC.
resultsIn both in vitro and in vivo hypothalamic cells, LC-MS/MS revealed the sequence of hundreds of neuropeptides as a resource for the field. Although the existence of β-melanocyte stimulating hormone (MSH) is controversial, we found that both this peptide and desacetyl α-MSH (d-α-MSH) were produced in considerable excess of acetylated α-MSH. In hPSC-derived hypothalamic neurons, these POMC derivatives were appropriately trafficked, secreted, and their production was significantly (P < 0.0001) increased in response to the hormone leptin.
conclusionsOur findings challenge the assumed pre-eminence of α-MSH and suggest that in humans, d-α-MSH and β-MSH are likely to be the predominant physiological products acting on melanocortin receptors.
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Registered trials
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