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Mitochondrial bioenergetics, uncoupling protein-2 activity, and reactive oxygen species production in the small intestine of a TNBS-induced colitis rat model

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Abstract

Inflammatory bowel disease (IBD) is often associated with a decrease in energy-dependent nutrient uptake across the jejunum that serves as the main site for absorption in the small intestine. This association has prompted us to investigate the bioenergetics underlying the alterations in jejunal absorption in 2,4,6-trinitrobenzenesulfonic acid-induced colitis in rats. We have found that mitochondrial oxygen consumption did not change in state 2 and state 3 respirations but showed an increase in state 4 respiration indicating a decrease in the respiratory control ratio of jejunal mitochondria during the peak of inflammation. This decrease in the coupling state was found to be guanosine diphosphate-sensitive, hence, implicating the involvement of uncoupling protein-2 (UCP2). Furthermore, the study has reported that the production of reactive oxygen species (ROS), known to be activators of UCP2, correlated negatively with UCP2 activity. Thus, we suggest that ROS production in the jejunum might be activating UCP2 which has an antioxidant activity, and that uncoupling of the mitochondria decreases the efficiency of energy production, leading to a decrease in energy-dependent nutrient absorption. Hence, this study is the first to account for an involvement of energy production and a role for UCP2 in the absorptive abnormalities of the small intestine in animal models of colitis.

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Acknowledgements

We thank Samira Osman for technical assistance. This study was funded by the Faculty of Medicine and Medical Sciences, University of Balamand.

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  1. Yara Al Ojaimi and Maha Khachab have contributed equally to this work and should be considered as joint first authors.

Authors and Affiliations

  1. Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Kalhat, Al-Kurah, Lebanon

    Yara Al Ojaimi, Maha Khachab, Georges M. Bahr & Karim S. Echtay

  2. Department of Biology, Faculty of Arts and Sciences, University of Balamand, Kalhat, Al-Kurah, Lebanon

    Samer Bazzi

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  1. Yara Al Ojaimi
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Contributions

MK, GMB, and KSE designed the study. YAO carried out the experiments. YAO, MK, SB, GMB, and KSE analyzed the data. YAO wrote the first draft of the manuscript and MK, SB, GMB, and KSE revised it. All authors have approved the final version of the manuscript.

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Correspondence to Karim S. Echtay.

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Al Ojaimi, Y., Khachab, M., Bazzi, S. et al. Mitochondrial bioenergetics, uncoupling protein-2 activity, and reactive oxygen species production in the small intestine of a TNBS-induced colitis rat model. Mol Cell Biochem 470, 87–98 (2020). https://doi.org/10.1007/s11010-020-03749-z

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