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

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Item Type:	Article
Title:	Cardiac phenotype and tissue sodium content in adolescents with defects in the melanocortin system
Creators Name:	Puder, L., Roth, S., Krabusch, P., Wiegand, S., Opitz, R., Bald, M., Flück, C., Schulz, E., Voss, E., Markó, L., Linz, P., Berger, F., Müller, D.N., Kuehne, T., Litt, M.J., Cone, R.D., 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
Additional Information:	Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
Official Publication:	https://doi.org/10.1210/clinem/dgab368
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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