Role of Carbohydrate response element-binding protein in mediating dexamethasone-induced glucose transporter 5 expression in Caco-2BBE cells and during the developmental phase in mice

ABSTRACT

Glucose transporter 5 (GLUT5), the main fructose transporter in mammals, is primarily responsible for absorbing dietary fructose in the small intestine. The expression of this intestinal gene significantly increases in response to developmental and dietary cues that reach the glucocorticoid receptor and carbohydrate response element-binding protein (ChREBP), respectively. Our study demonstrates that ChREBP is involved in the dexamethasone (Dex)-induced expression of GLUT5 in Caco-2BBE cells and the small intestine of both wild-type and ChREBP-knockout mice. Dex, a glucocorticoid, demonstrated an increase in GLUT5 mRNA levels in a dose- and time-dependent manner. While the overexpression of ChREBP moderately increased GLUT5 expression, its synergistic increase in the presence of Dex was noteworthy, whereas the suppression of ChREBP significantly reduced Dex-induced GLUT5 expression. Dex did not increase ChREBP protein levels but facilitated its nuclear translocation, thereby increasing the activity of the GLUT5 promoter. In vivo experiments conducted on 14-day-old mice pups treated with Dex for three days revealed that only wild-type mice (not ChREBP-knockout mice) exhibited Dex-mediated Glut5 gene induction, which further supports the role of ChREBP in regulating GLUT5 expression. Collectively, our results provide insights into the molecular mechanisms involved in the regulation of GLUT5 expression in response to developmental and dietary signals mediated by glucocorticoids and ChREBP.

General significance: The transcription factor ChREBP is important for Dex-mediated Glut5 gene expression in the small intestine.

KEYWORDS:

• Fructose transporter
• glucocorticoid hormone
• dexamethasone
• ChREBP
• small intestine

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization, J-YC, H-JL, and SH; data curation, J-YC; funding acquisition, SH and J-YC; investigation, SH, SP, H-JL, and J-YC; methodology, SH, JK, A-RO and J-YC; writing-draft preparation, SH and J-YC; writing-review and editing, SH, H-JL, and J-YC. All the authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This work was funded by the Basic Science Research Program through the National Research Foundation, by the Ministry of Education [grand number: 2022R1I1A1A01071897] to SH, and by the Ministry of Education, Science, and Technology [grand number: 2022R1A2C1012833] to J-YC.