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

Abstract

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.