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Cardiac phenotype and tissue sodium content in adolescents with defects in the melanocortin system

Item Type:Article
Title:Cardiac phenotype and tissue sodium content in adolescents with defects in the melanocortin system
Creators Name:Puder, L. and Roth, S. and Krabusch, P. and Wiegand, S. and Opitz, R. and Bald, M. and Flück, C. and Schulz, E. and Voss, E. and Markó, L. and Linz, P. and Berger, F. and Müller, D.N. and Kuehne, T. and Litt, M.J. and Cone, R.D. and Kühnen, P. and Kelm, M.
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. PARTICIPANTS: 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 (23)Na-MRI. RESULTS: Monogenic obese patients with POMC or MC4R mutation respectively had a significantly lower left ventricular mass/body surface area (BSA) compared to non-monogenic obese patients. Left ventricular end-diastolic volume/BSA was significantly lower in POMC- and MC4R-deficient patients than in non-monogenic obese patients. Subcutaneous fat and skin Na(+) content was significantly higher in POMC- and MC4R-deficient patients compared to non-monogenic obese patients. In these compartments, the water content was significantly higher in patients with POMC and MC4R mutation than in control-groups. CONCLUSIONS: 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 compared to non-monogenic obese patients. The results point towards the role of the melanocortin pathway for cardiac function, tissue Na(+) storage and the importance of including cardiologic assessments into the diagnostic work-up of these patients.
Keywords:Monogenic Obesity, POMC, MC4R, Melanocortin Pathway, Cardiac Function, Left-Ventricular Function, Tissue Sodium Content, Tissue Water Content
Source:Journal of Clinical Endocrinology and Metabolism
ISSN:0021-972X
Publisher:Endocrine Society
Volume:106
Number:9
Page Range:2606–2616
Date:September 2021
Official Publication:https://doi.org/10.1210/clinem/dgab368
PubMed:View item in PubMed

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