ZBTB32 performs crosstalk with the glucocorticoid receptor and is crucial in glucocorticoid responses to starvation
Lise Van Wyngene,
Tineke Vanderhaeghen,
Ioanna Petta,
Steven Timmermans,
Katrien Corbeels,
Bart Van der Schueren,
Jolien Vandewalle,
Kelly Van Looveren,
Charlotte Wallaeys,
Melanie Eggermont,
Sylviane Dewaele,
Leen Catrysse,
Geert van Loo,
Rudi Beyaert,
Roman Vangoitsenhoven,
Toshinori Nakayama,
Jan Tavernier,
Karolien De Bosscher,
Claude Libert
Affiliations
Lise Van Wyngene
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Tineke Vanderhaeghen
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Ioanna Petta
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium; Department of Rheumatology, Ghent University, 9000 Ghent, Belgium
Steven Timmermans
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Katrien Corbeels
Department of Chronic Diseases and Metabolism – Endocrinology, KU Leuven, Leuven, Belgium
Bart Van der Schueren
Department of Chronic Diseases and Metabolism – Endocrinology, KU Leuven, Leuven, Belgium
Jolien Vandewalle
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Kelly Van Looveren
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Charlotte Wallaeys
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Melanie Eggermont
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Sylviane Dewaele
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Leen Catrysse
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
Geert van Loo
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium
Rudi Beyaert
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium
Roman Vangoitsenhoven
Department of Chronic Diseases and Metabolism – Endocrinology, KU Leuven, Leuven, Belgium
Toshinori Nakayama
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan
Jan Tavernier
Center for Medical Biotechnology, VIB Center for Medical Biotechnology, 9000 Ghent, Belgium; Cytokine Receptor Laboratory (CRL), Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, 3 Albert Baertsoenkaai, 9000 Ghent, Belgium
Karolien De Bosscher
Center for Medical Biotechnology, VIB Center for Medical Biotechnology, 9000 Ghent, Belgium; Translational Nuclear Receptor Research Lab, Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, 3 Albert Baertsoenkaai,9000 Ghent, Belgium
Claude Libert
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium; Corresponding author
Summary: The hypothalamic-pituitary-adrenal (HPA) axis forms a complex neuroendocrine system that regulates the body’s response to stress such as starvation. In contrast with the glucocorticoid receptor (GR), Zinc finger and BTB domain containing 32 (ZBTB32) is a transcription factor with poorly described functional relevance in physiology. This study shows that ZBTB32 is essential for the production of glucocorticoids (GCs) in response to starvation, since ZBTB32−/− mice fail to increase their GC production in the absence of nutrients. In terms of mechanism, GR-mediated upregulation of adrenal Scarb1 gene expression was absent in ZBTB32−/− mice, implicating defective cholesterol import as the cause of the poor GC synthesis. These lower GC levels are further associated with aberrations in the metabolic adaptation to starvation, which could explain the progressive weight gain of ZBTB32−/− mice. In conclusion, ZBTB32 performs a crosstalk with the GR in the metabolic adaptation to starvation via regulation of adrenal GC production.
