Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 25;44(2):115278.
doi: 10.1016/j.celrep.2025.115278. Epub 2025 Feb 7.

Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism

Jie An  1 , Inna Astapova  2 , Guofang Zhang  3 , Andrew L Cangelosi  1 , Olga Ilkayeva  3 , Hannah Marchuk  1 , Michael J Muehlbauer  1 , Tabitha George  1 , Joseph Brozinick  4 , Mark A Herman  2 , Christopher B Newgard  5
Affiliations
Free article

Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism

Jie An et al. Cell Rep. .
Free article

Abstract

The transcription factor carbohydrate response element binding protein (ChREBP) activates genes of glucose, fructose, and lipid metabolism in response to carbohydrate feeding. Integrated transcriptomic and metabolomic analyses in rats with GalNac-siRNA-mediated suppression of ChREBP expression in liver reveal other ChREBP functions. GalNac-siChREBP treatment reduces expression of genes involved in coenzyme A (CoA) biosynthesis, with lowering of CoA and short-chain acyl-CoA levels. Despite suppression of pyruvate kinase, pyruvate levels are maintained, possibly via increased expression of pyruvate and amino acid transporters. In addition, expression of multiple anaplerotic enzymes is decreased by GalNac-siChREBP treatment, affecting TCA cycle intermediates. Finally, GalNAc-siChREBP treatment suppresses late steps in purine and NAD synthesis, with increases in precursors and lowering of end products in both pathways. In sum, our study reveals functions of ChREBP beyond its canonical roles in carbohydrate and lipid metabolism to include regulation of substrate transport, mitochondrial function, and energy balance.

Keywords: CP: Metabolism; ChREBP; CoA; amino acids; lipids; metabolic regulation; nucleotides.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests C.B.N. is a member of the Global Diabetes Advisory Board at Eli Lilly. All experiments described in this paper were supported by the above-referenced NIH grants. Eli Lilly supplied the GalNAc-siRNA reagents for the studies under a materials transfer agreement at their cost, with no restrictions on publication of data. J.B. is a Lilly employee who collaborated on the project by providing guidance in the use of the GalNAc-siRNA reagents and assistance with interpretation of data generated in their use.

Update of

Substances

LinkOut - more resources