Inhibition of CCAT/Enhancer-Binding Protein B3 axis by 1-Piperidin Propionic Acid as a new targeted therapy of Non-Alcoholic Steatohepatitis

Oct 3, 2026

Non-Alcoholic Fatty Liver Disease (NAFLD) is a leading cause of chronic liver disease worldwide, progressing from simple steatosis to non-alcoholic steatohepatitis (NASH). SerpinB3, proposed as a hepatokine, may modulate inflammation, fibrosis, and insulin resistance during NASH development. The study evaluates a targeted SerpinB3 inhibitor, 1-Piperidin Propionic Acid (1-PPA), in vitro and in vivo NASH models, assessing histology and expression of pro-fibrotic and pro-inflammatory markers.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages1

Reading Time3 min

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Introduction

Aim

Method

Conclusions

Results

I n h i b i t i o n o f C C A T / E n h a n c e r-B i n d i n g P r o t e i n b e t a - S e r p i n B 3 a x i s b y 1-P i p e r i d i n e P r o p i o n i c A c i d a s a n e wt a r g e t t h e r a p y o f N o n-A l c o h o l i c S t e a t o h e p a t i t i s F. PROTOPAPA 1 , G. M. VILLANO2 , E. NOVO 1 , C. TURATO4 , S.QUARTA 3 , M. G. RUVOLETTO 3 , A. BIASIOLO 3 , M. CHINELLATO 3 , A. MARTINI 3 , E. TREVELLIN 3 , M. GRANZOTTO 3 , S. CANNITO 1 , L. CENDRON 5 , S. DE SIERVI4 , 3M. GUIDO 3 , M. PAROLA 1 , R. VETTOR 3 , P. PONTISSO 3 1Department of Clinical and Biological Sciences, University of Torino, Italy; 2Department of Surgical, Oncological and Gastroenterological Sciences; University of Padova, Italy; 3Department of Medicine, University of Padova, Italy; 4Department of Molecular Medicine, University of Pavia, Italy; 5Department of Biology, University of Padova, Italy. Introduction Non-Alcoholic Fatty Liver Disease (NAFLD) is becoming the major cause of chronic liver disease worldwide, with a 25% prevalence in the general population and a higher prevalence in obese and type II diabetes patients. NAFLD includes a spectrum of liver diseases ranging from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH) . The serine protease inhibitor SerpinB3 has been proposed as a novel hepatokine able to modulate liver inflammation, fibrosis as well as insulin resistance during NASH development Aim In the present study, in order to investigate a new targeted therapeutic strategy for NASH, we have tested a specific SerpinB3 inhibitor, the 1-Piperidin Propionic Acid (1-PPA) PPA in in vitro and in vivo models of NASH Method In vivo models: analysis of histological parameters and gene expression of pro-fibrotic and pro-inflammatory markers in SerpinB3-transgenic (TG) fed on CDAA diet to induce experimental NASH and injected or not with 1-PPA (70 ng/g) . In vitro models: pro-fibrotic and pro-inflammatory genes were assessed in LX2 and THP1 cell lines, exposed to human SerpinB3 (100ng/ml) alone or with 1-PPA (100ng/ml) after 24 hours incubation Conclusions SerpinB3-C/EBP-β axis could be relevant in the development of NASH and the SerpinB3 inhibitor 1-PPA is effective in the control of inflammation and fibrosis in vitro and in NASH models, supporting this approach for a targeted therapy of NASH Acknowledgements We sincerely thank all the authors for their precious contribution Contact information Francesca Protopapa, PhD student Email: francesca.protopapa@unito.it Department of Clinical and Biological Sciences, University of Torino, Italy 1 2 3 5 6 7 Results 10x WT CDAA + PPA TG CDAA TG CDAA + PPA 2^ -DD ct Figure 1: In TG/SB3 mice fed on CDAA diet 1-PPA administration reduces inflammatory infiltration 4 3 2 1 0 WT TG 2^ -DD ct WT TG 2^ -DD ct CDAA CDAA + PPA 6 4 2 0 WT TG Figure 2: In TG/SB3 mice fed on CDAA diet 1-PPA administration reduces inflammatory mediators transcript levels WT CDAA WT CDAA + PPA TG CDAA TG CDAA + PPA Figure 3: In TG/SB3 mice fed on CDAA diet 1-PPA administration reduces significantly fibrosis 2^ -DD ct 15 10 5 0 a-SMA WT TG 2^ -DD ct 25 20 15 10 5 0 WT TG 2^ -DDct CDAA CDAA + PPATGF-b WT TG Figure 4: In TG/SB3 mice fed on CDAA diet 1-PPA administration down-regulates the transcript levels offibrotic mediators Scan to download the poster DOI: [10.3252/pso.eu.EASLCONGRESS.2023](10.3252/pso.eu.EASLCONGRESS.2023) Metabo lism, a lcohol and toxicity Francesca Proto papa EASL2023 WED--449-YI

FAQs

What condition is addressed in this study?

The study focuses on Non-Alcoholic Steatohepatitis (NASH), a progression of Non-Alcoholic Fatty Liver Disease (NAFLD).

What is the targeted therapeutic strategy tested?

It tests a specific SerpinB3 inhibitor, 1-Piperidin Propionic Acid (1-PPA), as a targeted therapy for NASH.

How was 1-PPA evaluated in the study?

Histological parameters and gene expression of pro-fibrotic and pro-inflammatory markers were analyzed in vivo, and relevant gene expression was assessed in cell lines in vitro after incubation with SerpinB3 ± 1-PPA.

Oct 3, 2026

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