Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells as Novel Diagnostic Tools for Non-Alcoholic Fatty Liver Disease: Visualizing Relationships with Known and Potential Disease Biomarkers

Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones.

Automated summary

Non-alcoholic fatty liver disease (NAFLD) is a global health emergency due to its high prevalence and lack of specific therapies. This study found that mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs) is associated with NAFLD, as indicated by reduced basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity in NAFLD patients compared to control subjects. These mitochondrial respiratory parameters were correlated with triglycerides, fasting insulin levels, IL-6 levels, HDL-cholesterol level, and fatty liver index, suggesting their potential as predictive biomarkers for NAFLD.