{"doi":"10.3389/fphys.2023.1172675","title":"Labeled breath tests in patients with NASH: Octanoate oxidation relates best to measures of glucose metabolism","abstract":"In vivo 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 13 C 4 -octanoate) and breath samples collected over 135 min. Total CO 2 production rates were measured using breath 13 CO 2 analysis by isotope ratio mass spectrometry. Fasting endogenous glucose production (EGP) was measured using an IV infusion of 13 C 6 -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 ( r = −0.474, p = 0.017) and EGP ( r = −0.441, p = 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 ( p = 0.044), negatively related to reductions in EGP ( r = −0.401, p = 0.064), and tended to correlate with reduced fasting glucose ( r = −0.371, p = 0.090). Subjects exhibited reductions in steatosis ( p = 0.007) which tended to correlate with increased OctOx (% of dose/kg, r = −0.411, p = 0.058). Based on our findings, the use of an 13 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.","journal":"Frontiers in Physiology","year":2023,"id":368917,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1127677,"name":"Alisha M. Perry","orcid":null,"position":1,"is_corresponding":false},{"id":1127270,"name":"Talyia M. Fordham","orcid":"0009-0007-3201-5986","position":2,"is_corresponding":false},{"id":698810,"name":"Alberto A. Diaz‐Arias","orcid":null,"position":3,"is_corresponding":false},{"id":698285,"name":"Jamal A. Ibdah","orcid":"0000-0002-5646-9014","position":4,"is_corresponding":false},{"id":212851,"name":"R. Scott Rector","orcid":"0000-0001-9908-7123","position":5,"is_corresponding":false},{"id":372223,"name":"Elizabeth J. Parks","orcid":"0000-0001-5681-1097","position":6,"is_corresponding":false},{"id":266332,"name":"Justine M. Mucinski","orcid":"0000-0003-4432-6638","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T01:15:24.517012Z","pmid":"37153214","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}