Insulin resistance, postprandial GLP-1 and adaptive immunity are the main predictors of NAFLD in a homogeneous population at high cardiovascular risk.

<bold>Background and Aims: </bold>The role of the different factors associated with fatty liver is still poorly defined. We evaluated the relationships between liver fat content (LF) and metabolic, inflammatory and nutritional factors in a homogeneous cohort of individuals at high cardio-metabolic risk.<bold>Methods and Results: </bold>In 70 individuals with high waist circumference and at least one more criterion for metabolic syndrome enrolled in a nutritional intervention study, LF was evaluated at baseline by hepatic/renal echo intensity ratio (H/R), together with dietary habits (7-day dietary record), insulin sensitivity and β-cell function (fasting and OGTT-derived indices), fasting and postprandial plasma GLP-1 and lipoproteins, and plasma inflammatory markers. H/R correlated positively with fasting and OGTT plasma glucose and insulin concentrations, HOMA-IR and β-cell function, and IL-4, IL-17, IFN-γ, TNF-α, FGF and GCSF plasma concentrations (p < 0.05 for all), and negatively with insulin sensitivity (OGIS), dietary, polyphenols and fiber (p < 0.05 for all). By multiple stepwise regression analysis, the best predictors of H/R were OGIS (β = -0.352 p = 0.001), postprandial GLP-1 (β = -0.344; p = 0.001), HDL-cholesterol (β = -0.323; p = 0.002) and IFN-γ (β = 0.205; p = 0.036).<bold>Conclusion: </bold>A comprehensive evaluation of factors associated with liver fat, in a homogeneous population at high cardio-metabolic risk, indicated a pathogenic combination of the same pathways underlying the atherosclerotic process, namely whole body insulin sensitivity and inflammation. The higher predictive value of postprandial variables suggests that liver fat is essentially a postprandial phenomenon, with a relevant role possibly played by GLP-1.<bold>Registration Number For Clinical Trials: </bold>NCT01154478. [ABSTRACT FROM AUTHOR]