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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Lim Homeobox 8 Is Essential for Beta Adrenergic Stimulation of Thermogenesis in Human Adipocytes

by
Katalin Gyurina
1,†,
Ádám Radványi
1,2,†,
László Sasi-Szabó
1,
Enikő Felszeghy
1,
Emese Rácz
3,
Gábor Méhes
3,
Andrea Kádár
4,
Csaba Fekete
4 and
Tamás Röszer
1,*
1
Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
2
Kálmán Laki Doctoral School, University of Debrecen, 4032 Debrecen, Hungary
3
Department of Pathology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
4
Laboratory of Integrative Neuroendocrinology, Hun-Ren Institute of Experimental Medicine, 1083 Budapest, Hungary
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2026, 15(11), 1000; https://doi.org/10.3390/cells15111000
Submission received: 4 May 2026 / Revised: 25 May 2026 / Accepted: 27 May 2026 / Published: 29 May 2026
(This article belongs to the Special Issue Adipose Tissue Functioning in Health and Diseases)
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Abstract

Catecholamines are crucial signaling molecules that initiate thermogenesis in adipocytes through beta-adrenergic receptors (ADRBs). Adipocyte catecholamine resistance is a common feature of pediatric obesity, often impeding weight loss and the maintenance of a healthy body fat percentage. Our aim was to identify possible mechanisms that may be responsible for the development of catecholamine resistance in adipocytes. We demonstrate that Lim homeobox 8 (LHX8), a transcription factor previously known for its role in gametogenesis, is essential for catecholamine-induced thermogenesis in human adipocytes. LHX8 is expressed in developing human adipocytes throughout intrauterine and perinatal life, as well as in adulthood, and its expression levels positively correlate with the expression of key thermogenesis genes. Pediatric obesity diminished adipocyte expression of LHX8. Functionally, ADRB stimulation failed to induce thermogenesis in both mouse and human adipocytes when LHX8 was absent. Conversely, LHX8 overexpression enhanced thermogenesis in murine adipocytes. Mechanistically, LHX8 stimulated adipocyte interleukin-33 (IL-33) synthesis in response to ADRB activation, which subsequently increased thermogenic gene expression in both human and mouse adipocytes. In conclusion, adipocyte LHX8 is indispensable for catecholamine-responsive thermogenesis and represents a promising novel therapeutic target to overcome catecholamine resistance and promote effective weight management.
Keywords: obesity; adipocyte; thermogenesis; uncoupling protein 1; interleukin-33 obesity; adipocyte; thermogenesis; uncoupling protein 1; interleukin-33
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MDPI and ACS Style

Gyurina, K.; Radványi, Á.; Sasi-Szabó, L.; Felszeghy, E.; Rácz, E.; Méhes, G.; Kádár, A.; Fekete, C.; Röszer, T. Lim Homeobox 8 Is Essential for Beta Adrenergic Stimulation of Thermogenesis in Human Adipocytes. Cells 2026, 15, 1000. https://doi.org/10.3390/cells15111000

AMA Style

Gyurina K, Radványi Á, Sasi-Szabó L, Felszeghy E, Rácz E, Méhes G, Kádár A, Fekete C, Röszer T. Lim Homeobox 8 Is Essential for Beta Adrenergic Stimulation of Thermogenesis in Human Adipocytes. Cells. 2026; 15(11):1000. https://doi.org/10.3390/cells15111000

Chicago/Turabian Style

Gyurina, Katalin, Ádám Radványi, László Sasi-Szabó, Enikő Felszeghy, Emese Rácz, Gábor Méhes, Andrea Kádár, Csaba Fekete, and Tamás Röszer. 2026. "Lim Homeobox 8 Is Essential for Beta Adrenergic Stimulation of Thermogenesis in Human Adipocytes" Cells 15, no. 11: 1000. https://doi.org/10.3390/cells15111000

APA Style

Gyurina, K., Radványi, Á., Sasi-Szabó, L., Felszeghy, E., Rácz, E., Méhes, G., Kádár, A., Fekete, C., & Röszer, T. (2026). Lim Homeobox 8 Is Essential for Beta Adrenergic Stimulation of Thermogenesis in Human Adipocytes. Cells, 15(11), 1000. https://doi.org/10.3390/cells15111000

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