{"doi":"10.1210/clinem/dgab368","title":"Cardiac Phenotype and Tissue Sodium Content in Adolescents With Defects in the Melanocortin System","abstract":"CONTEXT: Pro-opiomelanocortin (POMC) and the melanocortin-4 receptor (MC4R) play a pivotal role in the leptin-melanocortin pathway. Mutations in these genes lead to monogenic types of obesity due to severe hyperphagia. In addition to dietary-induced obesity, a cardiac phenotype without hypertrophy has been identified in MC4R knockout mice. OBJECTIVE: We aimed to characterize cardiac morphology and function as well as tissue Na+ content in humans with mutations in POMC and MC4R genes. METHODS: A cohort of 42 patients (5 patients with bi-allelic POMC mutations, 6 heterozygous MC4R mutation carriers, 19 obese controls without known monogenic cause, and 12 normal weight controls) underwent cardiac magnetic resonance (CMR) imaging and 23Na-MRI. RESULTS: Monogenic obese patients with POMC or MC4R mutation respectively had a significantly lower left ventricular mass/body surface area (BSA) than nonmonogenic obese patients. Left ventricular end-diastolic volume/BSA was significantly lower in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. Subcutaneous fat and skin Na+ content was significantly higher in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. In these compartments, the water content was significantly higher in patients with POMC and MC4R mutation than in control groups. CONCLUSION: Patients with POMC or MC4R mutations carriers had a lack of transition to hypertrophy, significantly lower cardiac muscle mass/BSA, and stored more Na+ within the subcutaneous fat tissue than nonmonogenic obese patients. The results point towards the role of the melanocortin pathway for cardiac function and tissue Na+ storage and the importance of including cardiologic assessments into the diagnostic work-up of these patients.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":202425,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":782462,"name":"Sophie Roth","orcid":"0000-0002-5334-2077","position":1,"is_corresponding":false},{"id":783083,"name":"Philipp Krabusch","orcid":null,"position":2,"is_corresponding":false},{"id":782463,"name":"Susanna Wiegand","orcid":"0000-0001-8341-9533","position":3,"is_corresponding":false},{"id":782464,"name":"Robert Opitz","orcid":"0000-0003-3143-0997","position":4,"is_corresponding":false},{"id":782465,"name":"Martin Bald","orcid":"0000-0003-3378-2160","position":5,"is_corresponding":false},{"id":617153,"name":"Christa E. Flück","orcid":null,"position":6,"is_corresponding":false},{"id":783084,"name":"Esther Schulz","orcid":null,"position":7,"is_corresponding":false},{"id":783085,"name":"Egbert Voß","orcid":null,"position":8,"is_corresponding":false},{"id":361363,"name":"Lajos Markó","orcid":"0000-0003-1888-5575","position":9,"is_corresponding":false},{"id":782466,"name":"Peter Linz","orcid":"0000-0002-8232-1443","position":10,"is_corresponding":false},{"id":729566,"name":"Felix Berger","orcid":"0000-0001-7881-1557","position":11,"is_corresponding":false},{"id":462024,"name":"Dominik N. Müller","orcid":"0000-0003-3650-5644","position":12,"is_corresponding":false},{"id":782467,"name":"Titus Kühne","orcid":"0000-0003-1631-4824","position":13,"is_corresponding":false},{"id":783086,"name":"M. Litt","orcid":null,"position":14,"is_corresponding":false},{"id":266180,"name":"Roger D. Cone","orcid":"0000-0003-3333-5651","position":15,"is_corresponding":false},{"id":782468,"name":"Peter Kühnen","orcid":"0000-0003-0211-176X","position":16,"is_corresponding":false},{"id":782469,"name":"Marcus Kelm","orcid":"0000-0003-4971-0452","position":17,"is_corresponding":false},{"id":783082,"name":"Lia Puder","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:51:10.291262Z","pmid":"34036349","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}