Cardiac Phenotype and Tissue Sodium Content in Adolescents With Defects in the Melanocortin System.

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 (2021). Cardiac Phenotype and Tissue Sodium Content in Adolescents With Defects in the Melanocortin System. The journal of clinical endocrinology and metabolism, 106(9), pp. 2606-2616. Oxford University Press 10.1210/clinem/dgab368

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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.

Item Type:

 Journal Article (Original Article)

Division/Institute:

 04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)

UniBE Contributor:

 Flück Pandey, Christa Emma

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 1945-7197

Publisher:

 Oxford University Press

Language:

 English

Submitter:

 Anette van Dorland

Date Deposited:

 07 Dec 2021 15:09

Last Modified:

 05 Dec 2022 15:55

Publisher DOI:

 10.1210/clinem/dgab368

PubMed ID:

 34036349

Uncontrolled Keywords:

 MC4R Monogenic obesity POMC cardiac function left ventricular function melanocortin pathway tissue sodium content tissue water content

BORIS DOI:

 10.48350/161518

URI:

 https://boris.unibe.ch/id/eprint/161518

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