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. 2022 Mar 8;14(6):1133.
doi: 10.3390/nu14061133.

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

Maria Principia Scavo  1 , Nicoletta Depalo  2 , Federica Rizzi  2   3 , Livianna Carrieri  1 , Grazia Serino  4 , Isabella Franco  5 , Caterina Bonfiglio  5 , Pasqua Letizia Pesole  6 , Raffaele Cozzolongo  7 , Vito Gianuzzi  7 , Maria Lucia Curri  2   3 , Alberto Ruben Osella  5 , Gianluigi Giannelli  8
Affiliations

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

Maria Principia Scavo et al. Nutrients. .

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.

Keywords: Frizzled 7; NAFLD; low glycemic index Mediterranean diet; physical activity; plasma-derived exosomes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Exosomes freshly extracted from plasma of healthy subjects (20) and NAFLD-affected patients (95, 56 males and 39 females) with moderate (38) or severe (57) hepatic steatosis at recruitment time (T0) and after treatment (T2): representative TEM micrographs obtained with staining, for two increasing staining times, namely, 30 (a1–e1) and 60 s (A–E) (scale bar 100 nm); intensity-average hydrodynamic diameter and corresponding polydispersity index (PDI) determined by DLS and ζ-potential value. Mean ± SD are reported, n = 3 (F).
Figure 2
Figure 2
Exosomes extracted from plasma of all healthy subjects (20) and NAFLD-affected patients (95) with moderate (38) or severe (57) hepatic steatosis at recruitment time (T0) and after treatment (T2): (A) representative Western Blotting of FZD7, ALIX, and HSP-70 (molecular mass markers are indicated on the right); (B) semi-quantitative estimation, by Western blotting analysis and densitometry of protein bands, of relative FZD7 expression level; (C) quantitative analysis of FZD7 by ELISA assay. For semiquantitative analysis, the same total protein content (20 µg) was loaded and FZD7 bands were evaluated upon normalization with the corresponding housekeeping ALIX protein band for each sample. * p < 0.05 and ** p < 0.001 versus control.
Figure 3
Figure 3
FZD7 expression and NAFLD contrasts (95% CI) by grade of severity. Number of healthy subjects (NAFLD absent) = 20, number of patients affected by moderate steatosis (NAFLD moderate) = 38, and severe steatosis (NAFLD Severe) = 57.
Figure 4
Figure 4
FDZ 7 expression and intervention arm: contrasts and 95% CI. The control group consisted of 20 subjects, the Inram diet group consisted of 16 subjects, the LGIMD group consisted of 17 subjects, the PA1 group consisted of 16 subjects, the PA2 group consisted of 14 subjects, the LGIMD + PA1 group consisted of 16 subjects, and the LGIMP + PA2 group consisted of 16 subjects.
Figure 5
Figure 5
FZD7 mRNA expression in liver tissue from NAFLD patients. (A) FZD7 expression data were obtained from the analysis of RNA sequencing of liver tissue from the 72 patients with severe NAFLD and from the 6 controls, downloaded from Gene Expression Omnibus database (GSE130970). (B) FZD7 expression data in the same cohort of NAFLD patients divided according to steatosis grade, including the 42 patients with moderate NAFLD and 71 with severe NAFLD. Mean expression data were expressed in TPM (transcripts per million). * p < 0.05.
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References

    1. Ibrahim S.H., Hirsova P., Gores G.J. Non-alcoholic steatohepatitis pathogenesis: Sublethal hepatocyte injury as a driver of liver inflammation. Gut. 2018;67:963–972. doi: 10.1136/gutjnl-2017-315691. - DOI - PMC - PubMed
    1. Adams L.A., Anstee Q.M., Tilg H., Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017;66:1138–1153. doi: 10.1136/gutjnl-2017-313884. - DOI - PubMed
    1. Vanhoutte P.M. Endothelial dysfunction: The first step toward coronary arteriosclerosis. Circ. J. 2009;73:595–601. doi: 10.1253/circj.CJ-08-1169. - DOI - PubMed
    1. Mittal S., El-Serang H.B., Sada Y.H., Kanwal F., Duan Z., Temple S., May S.B., Kramer J.R., Richardson P.A., Davila J.A. Hepatocellular carcinoma in the absence of cirrhosis in United States Veterans is associated with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2016;14:124–131.e1. doi: 10.1016/j.cgh.2015.07.019. - DOI - PMC - PubMed
    1. Nejak-Bowen K., Monga S.P. Wnt/beta-catenin signaling in hepatic organogenesis. Organogenesis. 2008;4:92–99. doi: 10.4161/org.4.2.5855. - DOI - PMC - PubMed