Van Wyngene Lise, Vanderhaeghen Tineke, Petta Ioanna, Timmermans Steven, Corbeels Katrien, Van der Schueren Bart, Vandewalle Jolien, Van Looveren Kelly, Wallaeys Charlotte, Eggermont Melanie, Dewaele Sylviane, Catrysse Leen, van Loo Geert, Beyaert Rudi, Vangoitsenhoven Roman, Nakayama Toshinori, Tavernier Jan, De Bosscher Karolien, Libert Claude
Center for Inflammation Research, VIB Center for Inflammation Research, 9000 Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
iScience. 2021 Jun 28;24(7):102790. doi: 10.1016/j.isci.2021.102790. eCollection 2021 Jul 23.
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 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.
下丘脑-垂体-肾上腺（HPA）轴构成一个复杂的神经内分泌系统，调节身体对饥饿等应激的反应。与糖皮质激素受体（GR）不同，含锌指和BTB结构域32（ZBTB32）是一种转录因子，其在生理学中的功能相关性鲜有描述。本研究表明，ZBTB32对于饥饿时糖皮质激素（GCs）的产生至关重要，因为ZBTB32基因敲除小鼠在缺乏营养时无法增加其GC生成。就机制而言，ZBTB32基因敲除小鼠中不存在GR介导的肾上腺基因表达上调，这意味着胆固醇摄取缺陷是GC合成不良的原因。这些较低的GC水平还与饥饿代谢适应异常有关，这可以解释ZBTB32基因敲除小鼠的体重逐渐增加。总之，ZBTB32通过调节肾上腺GC生成，在饥饿代谢适应过程中与GR进行相互作用。
