Different Associations of Plasma Lipopolysaccharide and Lipopolysaccharide-Binding Protein Concentrations with the Deterioration of Energy Metabolism from Healthy Individuals to Patients with Non-Alcoholic Fatty Liver Disease

<b>Background</b>: Energy metabolism progressively deteriorates from a healthy state to non-alcoholic fatty liver disease (NAFLD), and circulating lipopolysaccharide (LPS) may contribute to this process. However, previous studies have analyzed healthy individuals and NAFLD patients together, leaving stage-specific associations unclear. Whether LPS and its surrogate marker, lipopolysaccharide-binding protein (LBP), show similar relationships during NAFLD development also remains unknown. This study evaluated the associations between plasma LPS and LBP concentrations with clinical parameters in healthy individuals and NAFLD patients. <b>Methods</b>: We conducted a cross-sectional study of 31 healthy individuals (median age [IQR]: 31 (26-43) years) and 31 NAFLD patients (59 (54-70) years). Plasma LPS and LBP concentrations and clinical parameters were measured. Correlations were assessed using Spearman's rank analysis, followed by multivariate regression adjusting for age, sex, and BMI. <b>Results</b>: Plasma LPS and LBP concentrations were significantly higher in NAFLD patients compared to healthy individuals. Additionally, in the univariate regression analysis for all study participants, plasma LPS concentrations were correlated with obesity, blood pressure, liver function, lipid metabolism, and glucose metabolism. Plasma LBP concentrations were also correlated with age, obesity, blood pressure, liver function, lipid metabolism, glucose metabolism, and inflammatory cytokines. In healthy individuals, LPS correlated positively with triglycerides (TG), remaining significant after adjustment and exclusion of participants with any clinical test values outside the normal range. This association was not observed in NAFLD patients. Plasma LBP did not correlate with TG in either group; however, it was inversely associated with hepatic fat fraction in NAFLD patients, although this association was attenuated after adjusting for alanine aminotransferase. <b>Conclusions</b>: Plasma LPS correlates with TG even in clinically healthy individuals, suggesting LPS may influence lipid metabolism before NAFLD onset.