Acute High-Altitude Exposure Increases Transcription of Tricarboxylic Acid Cycle Enzymes in Human Duodenal Biopsies.

UNLABELLED: Strunz, Patrick-Pascal, Raphael N. Vuille-dit-Bille, Heiko Fruehauf, Mark Fox, Andreas Geier, Marco Maggiorini, Max Gassmann, Thomas A. Lutz, and Oliver Goetze. Acute high-altitude exposure increases transcription of tricarboxylic acid cycle enzymes in human duodenal biopsies. High Alt Med Biol. 27:184-188, 2026.

BACKGROUND

A recent study of our group quantifying 13C-octanoate metabolism in HA (Capanna Margherita [MG]/4,559 m) showed that acute HA exposure might lead to an increase of the lipolytic and CO2-producing pathways.

OBJECTIVE

To further test this hypothesis, we investigated intestinal biopsies from the same participants from simultaneously performed endoscopy studies for changes of mRNA-expression levels of the beta-oxidation enzymes and the decarboxylating tricarboxylic acid cycle (TCA) enzymes.

METHODS

Duodenal biopsies of 16 subjects exposed to HA were sampled via gastro-duodenoscopy at Zurich (baseline ZH, 490 m), on day 2 (MG2) and on day 4 at HA (MG4). After mRNA extraction, quantitative real-time polymerase chain reaction was performed to assess mRNAs expression of TCA cycle enzymes as well as beta-oxidation enzymes.

RESULTS

Aconitase mRNA levels increased early (MG2 vs. ZH, p < 0.05) and were still higher at day 4 compared with ZH (MG4 vs. ZH, p < 0.05). Isocitrate dehydrogenase (DH) levels increased with time spent at 4,559 m (MG4 vs. ZH, p < 0.01). The remaining TCA cycle and beta-oxidation enzymes investigated tended to higher values at HA but without reaching significance.

CONCLUSION

We conclude that acute exposure to HA leads to increased transcription of aconitase and isocitrate DH in the duodenal mucosa due to hypobaric hypoxia exposure.