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

Gian Paolo Caviglia,Maria Lorena Abate,Chiara Rosso,Elisabetta Bugianesi,Fabrizia Carli,Antonella Olivero,Amalia Gastaldelli,Davide Giuseppe Ribaldone,Giorgio Maria Saracco,Angelo Armandi,Melania Gaggini

doi:10.3390/ijms21228838

Gian Paolo Caviglia, Maria Lorena Abate + Show 9 more

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https://doi.org/10.3390/ijms21228838

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Abstract

Background: 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. Methods: 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. Results: Circulating SeP correlated with insulin (rS = 0.28), FFAs (rS = 0.42), glucose Rd (rS = −0.33) and glycerol Ra (rS = −0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (rS > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (rS = −0.31), glycine (rS = −0.44) and branched chain AA (rS = −0.32), and directly correlated with saturated (rS = 0.41) and monounsaturated FFAs (rS = 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, p = 0.022). Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD.

Highlights

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries alongside the increased incidence of obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome
The whole cohort has been grouped according to selenoprotein P (SeP) tertile and the 75th percentile has been used as the higher cut-off value
A diagnosis of non-alcoholic steatohepatitis (NASH) according to the joint presence of hepatic steatosis, ballooning and lobular inflammation was made in the majority of the patients (74%), even if advanced fibrosis (F ≥ 2) and severe fibrosis (F ≥ 3) were found in 57% and 27% of the cases, respectively (Table 1)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries alongside the increased incidence of obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome. The impaired lipolysis, due to adipose tissue IR, determines an increased flux of free fatty acids (FFAs) that reach the liver from the adipocytes and promote steatosis and enhances oxidative stress [7,8,9,10]. 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. Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD

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