Interplay between Oxidative Stress and Metabolic Derangements in Non-Alcoholic Fatty Liver Disease: The Role of Selenoprotein P.

Pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) are complex and multifactorial. We investigated oxidative stress through the measurement of selenoprotein P (SeP) in serum and we explored its relation to metabolic derangements and liver damage in a group of non-diabetic NAFLD subjects. 57 NAFLD patients underwent a double-tracer oral glucose tolerance test (OGTT). Insulin resistance (IR) components were calculated at baseline as follows: hepatic-IR = (endogenous glucose production*insulin); peripheral-IR = (glucose rate of disappearance(Rd)); adipose-tissue(AT)-IR as Lipo-IR = (glycerol rate of appearance (Ra)*insulin) or AT-IR = (free fatty acids (FFAs)*insulin). The lipid and amino acid (AA) profiles were assessed by gas chromatography-mass spectrometry. SeP levels were measured by enzyme immunosorbent assay. Circulating SeP correlated with insulin (r = 0.28), FFAs (r = 0.42), glucose Rd (r = -0.33) and glycerol Ra (r = -0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (r > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (r = -0.31), glycine (r = -0.44) and branched chain AA (r = -0.32), and directly correlated with saturated (r = 0.41) and monounsaturated FFAs (r = 0.40). Hepatic steatosis and fibrosis increased in subjects with higher levels of SeP. In multivariable regression analysis, SeP was associated with the degree of hepatic fibrosis (t = 2.4, = 0.022). SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD.