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- Title
Cardiac Phenotype and Tissue Sodium Content in Adolescents With Defects in the Melanocortin System.
- Authors
Puder, Lia; Roth, Sophie; Krabusch, Philipp; Wiegand, Susanna; Opitz, Robert; Bald, Martin; Flück, Christa; Schulz, Esther; Voss, Egbert; Markó, Lajos; Linz, Peter; Berger, Felix; Müller, Dominik N.; Kuehne, Titus; Litt, Michael J.; Cone, Roger D.; Kühnen, Peter; Kelm, Marcus
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>We aimed to characterize cardiac morphology and function as well as tissue Na+ content in humans with mutations in POMC and MC4R genes.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
LEPTIN receptors; PHENOTYPES; RENIN-angiotensin system; HEART; MAGNETIC resonance imaging; REGULATION of body weight; DISEASE risk factors; SODIUM metabolism; OBESITY complications; LEFT heart ventricle; WATER in the body; RESEARCH; GENETIC mutation; LEFT ventricular hypertrophy; RESEARCH methodology; CELL receptors; PROTEIN precursors; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; HEART physiology
- Publication
Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 9, p2606
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgab368