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174153

INSIGHTS INTO THE IMPACT OF FXR ACTIVATION ON HEPATIC AUTOPHAGY IN A NON-ALCOHOLIC STEATOHEPATITIS MODEL

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Last updated: 04 Jan 2025

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Abstract

Background: Multiple lines of evidence pointed to the role of dysbiosis, small intestinal bacterial overgrowth and altered intestinal permeability in promoting pro-inflammatory events in the liver leading to the progression of steatosis to non-alcoholic steatohepatitis (NASH). The pivotal involvement of farnesoid-X-receptor (FXR) in maintaining intestinal homeostasis and combating hepatic inflammation was previously established. Nonetheless, the role of hepatic autophagy in NASH pathogenesis and treatment remains controversial. The present study aimed at investigating whether the effect of the FXR agonist, obeticholic acid, on ameliorating NASH-related incidents is related to an impact on hepatic autophagy. Methods: Swiss albino mice were fed an atherogenic high fat diet (Ath-HFD) with dextran sulfate sodium (DSS) in drinking water to induce NASH. Obeticholic acid (5 mg/kg/day, p.o.) was given for 28 days, starting at day 64 post NASH initiation. Histopathological examination of liver and colon samples was performed. Inflammatory markers, IL-1β, IL-6, IFN-γ and TNF-α, besides adiponectin, were assessed in the liver. Autophagy genes, ULK1, BECN-1 and ATG5, were assessed by RT-PCR in hepatic tissues. Results: Histopathological changes observed in the liver and colon of the positive control group (Ath-HFD/DSS) were significantly ameliorated after treatment. No noticeable changes were reported in adiponectin and inflammatory markers following treatment except for a partial enhancement in IFN-γ. Though ULK1 and BECN-1 gene expression tended to increase after treatment with obeticholic acid compared to Ath-HFD/DSS group, ATG5 mRNA was almost restored. Conclusion: Obeticholic acid ameliorated NASH partially through autophagy and IFN-γ enhancements in the liver.

DOI

10.21608/bfsa.2021.174153

Authors

First Name

Rasha

Last Name

Tawfiq

MiddleName

A.

Affiliation

Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt

Email

rasha.tawfiq@bue.edu.eg

City

-

Orcid

-

First Name

Yasmeen

Last Name

Attia

MiddleName

M.

Affiliation

Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt

Email

yasmeen.attia@bue.edu.eg

City

-

Orcid

-

First Name

Noha

Last Name

Nassar

MiddleName

N.

Affiliation

Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

Email

noha.nassar@pharma.cu.edu.eg

City

-

Orcid

-

First Name

Olfat

Last Name

Hammam

MiddleName

A.

Affiliation

Department of Pathology, Theodor Bilharz Research Institute, Cairo, Egypt

Email

olfathammam@gmail.com

City

-

Orcid

-

First Name

Mohamed

Last Name

Elmazar

MiddleName

M.

Affiliation

Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt

Email

mohey.elmazar@bue.edu.eg

City

-

Orcid

-

First Name

Dalaal

Last Name

Abdallah

MiddleName

M.

Affiliation

Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

Email

dalaal.abdallah@pharma.cu.edu.eg

City

-

Orcid

-

Volume

44

Article Issue

1

Related Issue

25283

Issue Date

2021-06-01

Receive Date

2020-10-29

Publish Date

2021-06-01

Page Start

265

Page End

274

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 44_Issue 1_Pages 265-274.pdf

PDF . 2.6MB

Link

https://bpsa.journals.ekb.eg/article_174153.html

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https://bpsa.journals.ekb.eg/service?article_code=174153

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25

Type

Original Article

Type Code

1,096

Publication Type

Journal

Publication Title

Bulletin of Pharmaceutical Sciences Assiut University

Publication Link

https://bpsa.journals.ekb.eg/

MainTitle

INSIGHTS INTO THE IMPACT OF FXR ACTIVATION ON HEPATIC AUTOPHAGY IN A NON-ALCOHOLIC STEATOHEPATITIS MODEL

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Article

Created At

22 Jan 2023