Evolutionary conservation and divergence of regional fructose-responsive gene regulation in the intestine

Acute fructose challenge triggers regionally biased metabolic and stress gene regulation along the mouse and Drosophila intestine, with ChREBP/Mondo-Mlx as the major conserved regulator.

• Why it matters: Intestinal fructose catabolism is spatially organized, but it is unclear how zonation shapes fructose responses and which regulatory programs are evolutionarily conserved versus divergent.
• What they did: The study profiled regional gene regulation after acute fructose exposure across the small intestine in mouse and Drosophila, comparing ubiquitous versus proximodistal-biased targets and orthologous pathways.
• The result: ChREBP/Mondo-Mlx conserved activation of glucose metabolism, nutrient transport, and stress-responsive pathways, while downstream metabolic programs diverged: mouse favors fructose conversion to glucose, whereas Drosophila favors de novo lipogenesis.

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