Introduction An interaction between metabolic triggers and inherited predisposition underpins the development and progression of nonalcoholic Fatty Liver disease (NAFLD) and fatty liver disease in general. Among the specific NAFLD risk variants, PNPLA3 rs738409 C>G, encoding for the p.I148M protein variant, accounts for the largest fraction of liver disease heritability and is being intensively scrutinized. It promotes intrahepatic lipid accumulation and is associated with lipotoxicity and the more severe phenotypes, including fibrosis and carcinogenesis. Therefore, PNPLA3 appears as an appealing therapeutic target to counter NAFLD progression. Areas covered The scope of this review is to briefly describe the PNPLA3 gene and protein function before discussing therapeutic approaches for fatty liver aiming at this target. Literature review was carried out searching through PubMed and clinicaltrials.gov website and focusing on the most recent works and reviews. Expert opinion The main therapeutic strategies under development for NAFLD have shown variable efficacy and side-effects likely due to disease heterogeneity and lack of engagement of the main pathogenic drivers of liver disease. To overcome these limitations, new strategies are becoming available for targeting PNPLA3 p.I148M, responsible for a large fraction of disease susceptibility.

PNPLA3 as a therapeutic target for fatty liver disease : the evidence to date / A. Cherubini, E. Casirati, M. Tomasi, L.V.C. Valenti. - In: EXPERT OPINION ON THERAPEUTIC TARGETS. - ISSN 1472-8222. - (2021 Dec 14). [Epub ahead of print] [10.1080/14728222.2021.2018418]

PNPLA3 as a therapeutic target for fatty liver disease : the evidence to date

E. Casirati;L.V.C. Valenti
Ultimo
2021

Abstract

Introduction An interaction between metabolic triggers and inherited predisposition underpins the development and progression of nonalcoholic Fatty Liver disease (NAFLD) and fatty liver disease in general. Among the specific NAFLD risk variants, PNPLA3 rs738409 C>G, encoding for the p.I148M protein variant, accounts for the largest fraction of liver disease heritability and is being intensively scrutinized. It promotes intrahepatic lipid accumulation and is associated with lipotoxicity and the more severe phenotypes, including fibrosis and carcinogenesis. Therefore, PNPLA3 appears as an appealing therapeutic target to counter NAFLD progression. Areas covered The scope of this review is to briefly describe the PNPLA3 gene and protein function before discussing therapeutic approaches for fatty liver aiming at this target. Literature review was carried out searching through PubMed and clinicaltrials.gov website and focusing on the most recent works and reviews. Expert opinion The main therapeutic strategies under development for NAFLD have shown variable efficacy and side-effects likely due to disease heterogeneity and lack of engagement of the main pathogenic drivers of liver disease. To overcome these limitations, new strategies are becoming available for targeting PNPLA3 p.I148M, responsible for a large fraction of disease susceptibility.
PNPLA3; HSD17B13; Precision medicine; Nonalcoholic fatty liver disease; Liver organoids
Settore MED/03 - Genetica Medica
Article (author)
File in questo prodotto:
File Dimensione Formato  
PNPLA3 as a therapeutic target for fatty liver disease the evidence to date.pdf

embargo fino al 14/12/2022

Tipologia: Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione 1.67 MB
Formato Adobe PDF
1.67 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/889573
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact