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.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a novel term for Non-Alcoholic Fatty Liver Disease (NAFLD), is associated with liver mitochondrial dysfunction. We previously demonstrated that mitochondrial respiratory capacity in peripheral blood mononuclear cells (PBMCs) was significantly reduced in patients with MASLD compared to non-MASLD controls. For MASLD treatment, guidelines recommend behavioral and dietary changes to reduce body weight. A recent 12-month clinical trial demonstrated that ameliorating patients’ lifestyles through improved adherence to the Mediterranean diet and encouraged physical activity results in MASLD remission or regression. Methods: As a sub-study of the 12-month clinical trial, we evaluated the effects of the Mediterranean diet-oriented intervention on PBMC mitochondrial DNA content and respiratory parameters and on various biomarkers associated with MASLD. Results: Contrary to what was found at the baseline, after twelve months of intervention, systemic inflammatory and bioenergetics parameters did not differ between MASLD patients (N = 15) and control subjects (N = 17). PBMCs from MASLD subjects showed rescued basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. The observed recovery coincided with a significant increase in the patients’ adherence to the Mediterranean diet (Medscore). Conclusions: Our findings indicate that a Mediterranean diet-oriented intervention, without calorie reduction, preserves blood cell mitochondrial function in MASLD subjects. Thus, PBMC bioenergetics-based assays might be taken into account not only for diagnosing but also for monitoring therapeutic responses in MASLD.

Background/Objectives: Regular consumption of dietary fiber (DF) has been associated with non-communicable disease prevention and health benefits. As a result, having the ability to quickly and correctly estimate DF intake would allow the identification of at-risk groups and the development of public programs aimed at improving their intake. In this study, the authors translate and cross-culturally adapt a validated short food frequency questionnaire for the assessment of DF intake, thus adapting it to the Italian population. Methods: The process followed a six-step standardized protocol, and the pre-final version was tested among 40 volunteers. Six experts in nutrition performed the content validity study: Scale-level Content Validity Indexes based on Average (S-CVI/Ave) and Universal Agreement (S-CVI/UA) were calculated (cut-off = 0.83). Results: Both S-CVI/Ave and S-CVI/UA were 1.00 ± 0.0, higher than the cut-off value. The preliminary qualitative analysis showed an average DF intake of 21.5 ± 7.2 g/day, which is below the suggested national and international dietary targets, and mainly derives from fruits, vegetables, bread, and cereals. Based on their DF intake, subjects were classified as low (40%), moderate (37.5%), and high (22.5%) consumers. Conclusions: The translation and cross-cultural adaptation of a validated short food frequency questionnaire to assess DF intake provided us with a tool suitable for the Italian population. Its application in a real case has enabled the identification of three consumption classes, which can support the design of future studies and interventions.