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Neurotensin up-regulation is associated with advanced fibrosis and hepatocellular carcinoma in patients with MAFLD.

Authors :
Dongiovanni P
Meroni M
Petta S
Longo M
Alisi A
Soardo G
Valenti L
Miele L
Grimaudo S
Pennisi G
Antonio G
Consonni D
Fargion S
Fracanzani AL
Source :
Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2020 Oct; Vol. 1865 (10), pp. 158765. Date of Electronic Publication: 2020 Jul 11.
Publication Year :
2020

Abstract

Background & Aims: Neurotensin (NTS), a 13-aminoacid peptide localized in central nervous system and gastrointestinal tract, is involved in lipid metabolism and promotes various cancers onset mainly by binding to neurotensin receptor 1 (NTSR1). Increased plasma levels of pro-NTS, the stable NTS precursor, have been associated with type 2 diabetes (T2D), cardiovascular diseases and metabolic associated fatty liver disease (MAFLD). We aimed to evaluate 1) the impact of NTS rs1800832 and NTSR1 rs6090453 genetic variants on liver damage in 1166 MAFLD European individuals, 2) the relation between NTS variant and circulating pro-NTS and 3) the hepatic NTS expression by RNAseq transcriptomic analysis in 125 bariatric patients.<br />Results: The NTS rs1800832 G allele was associated with hepatic fibrosis (OR 1.27, 95% confidence interval (CI). 1.02-1.58; p = 0.03), even more in carriers of both NTS and NTSR1 G risk alleles (OR 1.17, 95% CI. 1.03-1.34; p = 0.01), with cirrhosis (OR 1.58, 95% CI. 1.07-2.34; p = 0.02) and HCC (OR 1.98, 95% CI. 1.24-3.2; p = 0.004). Pro-NTS circulating levels were correlated with T2D (p = 0.005), BMI, (p = 0.04), age (p = 0.0016), lobular inflammation (p = 0.0025), fibrosis>2 (p < 0.0001), cirrhosis (p = 0.0009) and HCC (p < 0.0001) and more so after stratification for the NTS G allele. Transcriptomic data showed that hepatic NTS expression correlated with that of fibrogenic genes (p < 0.05).<br />Conclusions: NTS rs1800832 variant is associated with advanced fibrosis and HCC in MAFLD patients likely affecting NTS protein activity. The rs6090453 NTSR1 gene variant synergizes with NTS rs1800832 mutation to promote liver damage. Prospective studies are necessary to confirm NTS role in liver disease progression.<br />Competing Interests: Declaration of competing interest None.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-2618
Volume :
1865
Issue :
10
Database :
MEDLINE
Journal :
Biochimica et biophysica acta. Molecular and cell biology of lipids
Publication Type :
Academic Journal
Accession number :
32663609
Full Text :
https://doi.org/10.1016/j.bbalip.2020.158765