Exosomal FZD-7 Expression Is Modulated by Different Lifestyle Interventions in Patients with NAFLD.

Vito Gianuzzi,Grazia Serino,Livianna Carrieri,Maria Principia Scavo,Federica Rizzi,Pasqua Letizia Pesole,Gianluigi Giannelli,Raffaele Cozzolongo,Caterina Bonfiglio,Isabella Franco,Alberto Ruben Osella,Maria Lucia Curri,Nicoletta Depalo

doi:10.3390/nu14061133

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.

Highlights

Non-alcoholic fatty liver disease (NAFLD), a multifactorial complex chronic condition, is considered a metabolic syndrome with hypertriglyceridemia and abnormal liver fat accumulation, without alcohol intake or use of steatogenic drugs
Exosomes were isolated from plasma of all the enrolled subjects, including the healthy subjects and the NAFLD-affected patients with moderate or severe hepatic steatosis at recruitment time (T0) and after 90 days of intervention (T2)
Data obtained by Western blotting analysis of plasma-derived exosomes from NAFLD

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD), a multifactorial complex chronic condition, is considered a metabolic syndrome with hypertriglyceridemia and abnormal liver fat accumulation, without alcohol intake or use of steatogenic drugs. The relevant contributions to the epidemiology of NAFLD has been attributed to overweight and obesity that represent the condition, resulting from sedentary lifestyle combined with unregulated diet. NAFLD starts as simple steatosis (NAFL), abnormal accumulation of toxic liver fat triggers inflammation, inducing the development of the so-called non-alcoholic steatohepatitis (NASH). NASH, a chronic state of liver inflammation, causes the transformation of hepatic stellate cells to myofibroblasts with the concomitant production of extra-cellular matrix (ECM), progressing in liver fibrosis. Advanced liver fibrosis represents a relevant risk factor for development of hepatocellular carcinoma (HCC), that HCC has been found in patients with NAFLD in the absence of cirrhosis [4]

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