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NUPR1 protects liver from lipotoxic injury by improving the endoplasmic reticulum stress response

Borrello, Maria Teresa, Emma, Maria Rita, Listi, Angela, Rubis, Marion, Coslet, Sergiu, Augello, Giuseppa, Cusiamano, Antonella, Cabibi, Daniela, Porcasi, Rossana, Giannitrapani, Lydia, Soresi, Maurizio, Pantuso, Gianni, Blyth, Karen, Montalto, Giuseppe, Pin, Christopher, Cervello, Melchiorre and Iovanna, Juan (2021) NUPR1 protects liver from lipotoxic injury by improving the endoplasmic reticulum stress response. FASEB. pp. 1-19. ISSN 1530-6860

Item Type: Article


Non-alcoholic fatty liver (NAFL) and related syndromes affect one-third of the adult population in industrialized and developing countries. Lifestyle and caloric oversupply are the main causes of such array of disorders, but the molecular mechanisms underlying their etiology remain elusive. Nuclear Protein 1 (NUPR1) expression increases upon cell injury in all organs including liver. Recently, we reported NUPR1 actively participates in the activation of the Unfolded Protein Response (UPR). The UPR typically maintains protein homeostasis, but downstream mediators of the pathway regulate metabolic functions including lipid metabolism. As increases in UPR and NUPR1 in obesity and liver disease have been well documented, the goal of this study was to investigate the roles of NUPR1 in this context. To establish whether NUPR1 is involved in these liver conditions we used patient-derived liver biopsies and in vitro and in vivo NUPR1 loss of functions models. First, we analyzed NUPR1 expression in a cohort of morbidly obese patients (MOPs), with simple fatty liver (NAFL) or more severe steatohepatitis (NASH). Next, we explored the metabolic roles of NUPR1 in wild-type (Nupr1+/+ ) or Nupr1 knockout mice (Nupr1-/- ) fed with a high-fat diet (HFD) for 15 weeks. Immunohistochemical and mRNA analysis revealed NUPR1 expression is inversely correlated to hepatic steatosis progression. Mechanistically, we found NUPR1 participates in the activation of PPAR-α signaling via UPR. As PPAR-α signaling is controlled by UPR, collectively, these findings suggest a novel function for NUPR1 in protecting liver from metabolic distress by controlling lipid homeostasis, possibly through the UPR.

The FASEB Journal - 2021 - Teresa Borrello - NUPR1 protects liver from lipotoxic injury by improving the endoplasmic.pdf - Published Version
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Uncontrolled Keywords: lipotoxicity, NAFL, NASH, NUPR1, PPAR-a signalling, UPR
Depositing User: Teresa Borrello


Item ID: 15970
Identification Number:
ISSN: 1530-6860
Official URL:

Users with ORCIDS

ORCID for Maria Teresa Borrello: ORCID iD

Catalogue record

Date Deposited: 05 May 2023 14:03
Last Modified: 05 May 2023 14:03


Author: Maria Teresa Borrello ORCID iD
Author: Maria Rita Emma
Author: Angela Listi
Author: Marion Rubis
Author: Sergiu Coslet
Author: Giuseppa Augello
Author: Antonella Cusiamano
Author: Daniela Cabibi
Author: Rossana Porcasi
Author: Lydia Giannitrapani
Author: Maurizio Soresi
Author: Gianni Pantuso
Author: Karen Blyth
Author: Giuseppe Montalto
Author: Christopher Pin
Author: Melchiorre Cervello
Author: Juan Iovanna

University Divisions

Faculty of Health Sciences and Wellbeing


Sciences > Health Sciences
Sciences > Nursing
Sciences > Pharmacy and Pharmacology

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