Betulin prevents high fat diet-induced non-alcoholic fatty liver disease by mitigating oxidative stress and upregulating Nrf2 and SIRT1 in rats

Farage, Amira E, Abdo, Walied, Osman, Amira, Abdel-Kareem, Mona A, Hakami, Zaki H, Alsulimani, Ahmad, Bin-Ammar, Albandari, Alanazi, Ashwag S, Alsuwayt, Bader, Alanazi, Mohammed M, Antar, Samar A, Kamel, Emadeldin M and Mahmoud, Ayman M (2023) Betulin prevents high fat diet-induced non-alcoholic fatty liver disease by mitigating oxidative stress and upregulating Nrf2 and SIRT1 in rats. Life Sciences, 322. 121688. ISSN 0024-3205

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Official URL: https://doi.org/10.1016/j.lfs.2023.121688

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder characterized by hepatic lipid accumulation. This study explored the effect of betulin (BE), a terpenoid with promising antioxidant, anti-inflammatory and insulin sensitizing effects, on NAFLD induced by high fat diet (HFD). Rats received HFD and BE (15 and 30 mg/kg) for 12 weeks and blood and liver samples were collected for analyses. HFD caused hyperlipidemia, cholesterol and triglycerides accumulation in the liver, hepatocellular ballooning, fibrosis, insulin resistance (IR), lipid peroxidation (LPO), and NF-kB p65 upregulation. BE ameliorated serum and liver lipids, blood glucose and insulin, liver LPO, prevented steatosis and fibrosis, suppressed NF-kB p65 and enhanced antioxidants in HFD-fed rats. BE downregulated acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS), and upregulated Nrf2, HO-1 and SIRT1 in the liver of HFD-fed rats. In silico investigations revealed the binding affinity of BE towards FAS, NF-kB, Keap1, HO-1 and SIRT1. In conclusion, BE attenuated HFD-induced NAFLD by ameliorating hyperlipidemia, IR, lipogenesis, liver lipid accumulation, and oxidative stress. The protective effect of BE was associated with enhanced Nrf2/HO-1 signaling and SIRT1.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	09 Nov 2023 16:31
Publisher:	Elsevier
Additional Information:	© 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
Divisions:	Faculties > Science and Engineering
Subject terms:	Liver, Animals, Rats, Insulin Resistance, Fibrosis, Triterpenes, Insulin, Lipids, NF-kappa B, Antioxidants, Oxidative Stress, NF-E2-Related Factor 2, Sirtuin 1, Diet, High-Fat, Non-alcoholic Fatty Liver Disease, Kelch-Like ECH-Associated Protein 1, Betulin, Dyslipidemia, Oxidative stress, SIRT1, Steatosis, Animals, Rats, Antioxidants, Diet, High-Fat, Fibrosis, Insulin, Insulin Resistance, Kelch-Like ECH-Associated Protein 1, Lipids, Liver, NF-E2-Related Factor 2, NF-kappa B, Non-alcoholic Fatty Liver Disease, Oxidative Stress, Sirtuin 1, Triterpenes, 0601 Biochemistry and Cell Biology, 1115 Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy
Data Access Statement:	The manuscript contains all data supporting the reported results.
URI:	https://e-space.mmu.ac.uk/id/eprint/633043
DOI:	https://doi.org/10.1016/j.lfs.2023.121688
ISSN	0024-3205
e-ISSN	1879-0631

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