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Exploring Liver Mitochondrial Function by 13C-Stable Isotope Breath Tests: Implications in Clinical Biochemistry

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Mitochondrial Regulation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2310))

Abstract

The liver is at the crossroad of key metabolic processes, which include detoxification, glycolipidic storage and export, and protein synthesis. The gut–liver axis, moreover, provides hepatocytes with a series of bacterial products and metabolites, which contribute to maintain liver function in health and disease. Breath tests (BTs) are developed as diagnostic tools for indirect, rapid, noninvasive assessment of several metabolic processes in the liver. BTs monitor the appearance of CO2 in breath as a marker of a specific substrate metabolized in the liver, typically within microsomes, cytosol, or mitochondria. The noninvasiveness of BTs originates from the use of the, nonradioactive, naturally occurring stable isotope 13C marking a specific substrate which is metabolized in the liver, leading to the appearance of 13CO2 in expired air. Some substrates (ketoisocaproic acid, methionine, and octanoic acid) provide information about dynamic liver mitochondrial function in health and disease. In humans, the application of 13C-breath tests ranges from nonalcoholic and alcoholic liver diseases to liver cirrhosis, hepatocarcinoma, preoperative and postoperative assessment of liver function, and drug-induced liver damage. 13C-BTs are an indirect, cost-effective, and easy method to evaluate dynamic liver function and gastric kinetics in health and disease, with ongoing studies focusing on further applications in clinical medicine.

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Acknowledgments

These projects received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 722619 (FOIE GRAS) and Grant Agreement No. 734719 (mtFOIE GRAS). EMM and HS are recipients of Marie Skłodowska-Curie Grant Agreement No. 722619. We thank Rosa De Venuto, Paola De Benedictis, and Michele Persichella for skillful technical support.

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Authors and Affiliations

  1. Clinica Medica “A. Murri”, Department of Biosciences and Human Oncology (DIMO), Policlinico Hospital, University of Bari Medical School, Bari, Italy

    Emilio Molina-Molina, Harshitha Shanmugam, Domenica Di Palo, Ignazio Grattagliano & Piero Portincasa

  2. Italian College of General Practitioners and Primary Care, Bari, Italy

    Ignazio Grattagliano

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  1. Emilio Molina-Molina
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  2. Harshitha Shanmugam
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  3. Domenica Di Palo
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  4. Ignazio Grattagliano
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  5. Piero Portincasa
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Correspondence to Piero Portincasa .

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  1. Department of Life Sciences, University of Coimbra, Coimbra, Portugal

    Carlos M. Palmeira

  2. Department of Life Sciences, University of Coimbra, Coimbra, Portugal

    Anabela P. Rolo

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Molina-Molina, E., Shanmugam, H., Di Palo, D., Grattagliano, I., Portincasa, P. (2021). Exploring Liver Mitochondrial Function by 13C-Stable Isotope Breath Tests: Implications in Clinical Biochemistry. In: Palmeira, C.M., Rolo, A.P. (eds) Mitochondrial Regulation. Methods in Molecular Biology, vol 2310. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1433-4_11

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