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Abdul Majeed, S.* ; Dunzendorfer, H.* ; Weiner, J.* ; Heiker, J.T. ; Kiess, W.* ; Körner, A. ; Landgraf, K.*

COBL, MKX and MYOC are potential regulators of brown adipose tissue development associated with obesity-related metabolic dysfunction in children.

Int. J. Mol. Sci. 24:20 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Obesity is already accompanied by adipose tissue (AT) dysfunction and metabolic disease in children and increases the risk of premature death. Due to its energy-dissipating function, brown AT (BAT) has been discussed as being protective against obesity and related metabolic dysfunction. To analyze the molecular processes associated with BAT development, we investigated genome-wide expression profiles in brown and white subcutaneous and perirenal AT samples of children. We identified 39 upregulated and 26 downregulated genes in uncoupling protein 1 (UCP1)-positive compared to UCP1-negative AT samples. We prioritized for genes that had not been characterized regarding a role in BAT biology before and selected cordon-bleu WH2 repeat protein (COBL), mohawk homeobox (MKX) and myocilin (MYOC) for further functional characterization. The siRNA-mediated knockdown of Cobl and Mkx during brown adipocyte differentiation in vitro resulted in decreased Ucp1 expression, while the inhibition of Myoc led to increased Ucp1 expression. Furthermore, COBL, MKX and MYOC expression in the subcutaneous AT of children is related to obesity and parameters of AT dysfunction and metabolic disease, such as adipocyte size, leptin levels and HOMA-IR. In conclusion, we identify COBL, MKX and MYOC as potential regulators of BAT development and show an association of these genes with early metabolic dysfunction in children.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cobl ; Mkx ; Myoc ; Adipocyte Differentiation ; Adipose Tissue ; Brown Adipose Tissue ; Children ; Metabolic Disease ; Obesity ; White Adipose Tissue; Transcription Factor Mohawk; Mesenchymal Stem-cells; Cordon-bleu; Thermogenic Adipocytes; Cold-exposure; Ppar-gamma; Gene; White; Differentiation; Identification
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 24, Heft: 4, Seiten: , Artikelnummer: 20 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)