Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease characterized by fat deposits in liver cells, which can lead to hepatitis and fibrosis. This study attempted to explore the protective effect of vitamin D3 (VitD) against NAFLD.Methods: Adult male albino rats were randomized...

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Main Authors: Doha Reda, Gehad E. Elshopakey, Talat A. Albukhari, Samah J. Almehmadi, Bassem Refaat, Engy F. Risha, Hebatallah A. Mahgoub, Mohamed E. El-Boshy, Fatma M. Abdelhamid
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1164512/full
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author Doha Reda
Gehad E. Elshopakey
Talat A. Albukhari
Samah J. Almehmadi
Bassem Refaat
Engy F. Risha
Hebatallah A. Mahgoub
Mohamed E. El-Boshy
Fatma M. Abdelhamid
author_facet Doha Reda
Gehad E. Elshopakey
Talat A. Albukhari
Samah J. Almehmadi
Bassem Refaat
Engy F. Risha
Hebatallah A. Mahgoub
Mohamed E. El-Boshy
Fatma M. Abdelhamid
author_sort Doha Reda
collection DOAJ
description Introduction: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease characterized by fat deposits in liver cells, which can lead to hepatitis and fibrosis. This study attempted to explore the protective effect of vitamin D3 (VitD) against NAFLD.Methods: Adult male albino rats were randomized into four separate groups: the negative control group was fed a standard rat chow; the positive group received a high-fat diet (20%) and 25% fructose water (NAFLD); the VitD control group was intramuscularly treated with VitD (1,000 IU/kg BW) 3 days per week for 10 weeks; and the NAFLD group was treated with VitD therapy. Biochemical and hepatic histological analyses were performed. Hepatic oxidative stress and inflammatory conditions were also studied. Hepatic expression of sterol regulatory element-binding protein 1-c (SREBP-1-c), peroxisome proliferator-activated receptor alpha (PPAR-α), and insulin receptor substrate-2 was analyzed by quantitative real-time polymerase chain reaction.Results and discussion: The NAFLD rats exhibited elevated terminal body weight, hepatic injury markers, dyslipidemia, glucose intolerance, and insulin resistance. Moreover, the NAFLD rats had increased SREBP-1-c expression and reduced PPAR-α and IRS-2 expressions. Histological analysis showed hepatic steatosis and inflammation in the NAFLD group. In contrast, VitD administration improved the serum biochemical parameters and hepatic redox status in NAFLD rats. Also, VitD treatment ameliorated hepatic inflammation and steatosis in the NAFLD group by decreasing the expression of SREBP-1-c and increasing the expression of PPAR-α. Overall, these results suggest that VitD could have a protective effect against NAFLD and its associated complication.
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spelling doaj.art-40081520b109483292e21d54f3de3b092023-05-16T05:16:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.11645121164512Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathwayDoha Reda0Gehad E. Elshopakey1Talat A. Albukhari2Samah J. Almehmadi3Bassem Refaat4Engy F. Risha5Hebatallah A. Mahgoub6Mohamed E. El-Boshy7Fatma M. Abdelhamid8Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptClinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptDepartment of Haematology and Immunology, Faculty of Medicine, Umm Alqura University, Makkah, Saudi ArabiaLaboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi ArabiaLaboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi ArabiaClinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptPathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptClinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptClinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptIntroduction: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease characterized by fat deposits in liver cells, which can lead to hepatitis and fibrosis. This study attempted to explore the protective effect of vitamin D3 (VitD) against NAFLD.Methods: Adult male albino rats were randomized into four separate groups: the negative control group was fed a standard rat chow; the positive group received a high-fat diet (20%) and 25% fructose water (NAFLD); the VitD control group was intramuscularly treated with VitD (1,000 IU/kg BW) 3 days per week for 10 weeks; and the NAFLD group was treated with VitD therapy. Biochemical and hepatic histological analyses were performed. Hepatic oxidative stress and inflammatory conditions were also studied. Hepatic expression of sterol regulatory element-binding protein 1-c (SREBP-1-c), peroxisome proliferator-activated receptor alpha (PPAR-α), and insulin receptor substrate-2 was analyzed by quantitative real-time polymerase chain reaction.Results and discussion: The NAFLD rats exhibited elevated terminal body weight, hepatic injury markers, dyslipidemia, glucose intolerance, and insulin resistance. Moreover, the NAFLD rats had increased SREBP-1-c expression and reduced PPAR-α and IRS-2 expressions. Histological analysis showed hepatic steatosis and inflammation in the NAFLD group. In contrast, VitD administration improved the serum biochemical parameters and hepatic redox status in NAFLD rats. Also, VitD treatment ameliorated hepatic inflammation and steatosis in the NAFLD group by decreasing the expression of SREBP-1-c and increasing the expression of PPAR-α. Overall, these results suggest that VitD could have a protective effect against NAFLD and its associated complication.https://www.frontiersin.org/articles/10.3389/fphar.2023.1164512/fullhepatic steatosisvitamin Dhigh-fat dietinsulin resistanceoxidative stress
spellingShingle Doha Reda
Gehad E. Elshopakey
Talat A. Albukhari
Samah J. Almehmadi
Bassem Refaat
Engy F. Risha
Hebatallah A. Mahgoub
Mohamed E. El-Boshy
Fatma M. Abdelhamid
Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway
Frontiers in Pharmacology
hepatic steatosis
vitamin D
high-fat diet
insulin resistance
oxidative stress
title Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway
title_full Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway
title_fullStr Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway
title_full_unstemmed Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway
title_short Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway
title_sort vitamin d3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the srebp 1 c pparα nf κb ir s2 signaling pathway
topic hepatic steatosis
vitamin D
high-fat diet
insulin resistance
oxidative stress
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1164512/full
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