AUTHOR=Mucinski Justine M. , Perry Alisha M. , Fordham Talyia M. , Diaz-Arias Alberto , Ibdah Jamal A. , Rector R. Scott , Parks Elizabeth J. 

TITLE=Labeled breath tests in patients with NASH: Octanoate oxidation relates best to measures of glucose metabolism

JOURNAL=Frontiers in Physiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1172675

DOI=10.3389/fphys.2023.1172675

ISSN=1664-042X

ABSTRACT=<p><italic>In vivo</italic> methods to estimate human liver mitochondrial activity are lacking and this project’s goal was to use a non-invasive breath test to quantify complete mitochondrial fat oxidation and determine how test results changed when liver disease state was altered over time. Patients with suspected non-alcoholic fatty liver disease (NAFLD; 9 men, 16 women, 47 ± 10 years, 113 ± 23 kg) underwent a diagnostic liver biopsy and liver tissue was histologically scored by a pathologist using the NAFLD activity score (0–8). To assess liver oxidation activity, a labeled medium chain fatty acid was consumed orally (23.4 mg <sup>13</sup>C<sub>4</sub>-octanoate) and breath samples collected over 135 min. Total CO<sub>2</sub> production rates were measured using breath <sup>13</sup>CO<sub>2</sub> analysis by isotope ratio mass spectrometry. Fasting endogenous glucose production (EGP) was measured using an IV infusion of <sup>13</sup>C<sub>6</sub>-glucose. At baseline, subjects oxidized 23.4 ± 3.9% (14.9%–31.5%) of the octanoate dose and octanoate oxidation (OctOx) was negatively correlated with fasting plasma glucose (<italic>r</italic> = −0.474, <italic>p</italic> = 0.017) and EGP (<italic>r</italic> = −0.441, <italic>p</italic> = 0.028). Twenty-two subjects returned for repeat tests 10.2 ± 1.0 months later, following lifestyle treatment or standardized care. OctOx (% dose/kg) was significantly greater across all subjects (<italic>p</italic> = 0.044), negatively related to reductions in EGP (<italic>r</italic> = −0.401, <italic>p</italic> = 0.064), and tended to correlate with reduced fasting glucose (<italic>r</italic> = −0.371, <italic>p</italic> = 0.090). Subjects exhibited reductions in steatosis (<italic>p</italic> = 0.007) which tended to correlate with increased OctOx (% of dose/kg, <italic>r</italic> = −0.411, <italic>p</italic> = 0.058). Based on our findings, the use of an <sup>13</sup>C-octanoate breath test may be an indicator of hepatic steatosis and glucose metabolism, but these relationships require verification through larger studies in NAFLD populations.</p>