Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxida...

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Autores principales:	Zaida Zakaria, Zaidatul Akmal Othman, Joseph Bagi Suleiman, Nur Asyilla Che Jalil, Wan Syaheedah Wan Ghazali, Mahaneem Mohamed
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Keap1 metabolic syndrome NAFLD Nrf2 orlistat oxidative stress parameters Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/1b09adb6c145429d9726a57c523c48b7
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spelling	oai:doaj.org-article:1b09adb6c145429d9726a57c523c48b72021-11-25T19:12:04ZProtective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation10.3390/vetsci81102742306-7381https://doaj.org/article/1b09adb6c145429d9726a57c523c48b72021-11-01T00:00:00Zhttps://www.mdpi.com/2306-7381/8/11/274https://doaj.org/toc/2306-7381Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress parameters in high-fat diet (HFD) induced-MAFLD rats. Twenty-four male <i>Sprague-Dawley</i> rats were randomly divided into four groups (<i>n</i> = 6/group), i.e., Normal control (N), HFD, HFD + orlistat (HFD + O) (10 mg/kg/day administered concomitantly for 12 weeks as a protective model), and obese+orlistat (OB + O) (10 mg/kg/day administered 6 weeks after induction of obesity as a therapeutic model) groups. After 12 weeks, the HFD group had significantly increased Lee obesity index, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein levels, liver total cholesterol and triglyceride levels, insulin resistance and non-alcoholic steatohepatitis (NASH) together with decreased serum high-density lipoprotein level. Additionally, the HFD group also showed increased Nrf2 translocation to the nucleus with high Keap1 expression and increased liver oxidative stress parameters. Orlistat significantly improved all these alterations in HFD rats. We demonstrated that orlistat might have protective and therapeutic effects against HFD-induced MAFLD rats by its activation on Nrf2 signaling pathway, which subsequently improved metabolic syndrome and oxidative stress parameters.Zaida ZakariaZaidatul Akmal OthmanJoseph Bagi SuleimanNur Asyilla Che JalilWan Syaheedah Wan GhazaliMahaneem MohamedMDPI AGarticleKeap1metabolic syndromeNAFLDNrf2orlistatoxidative stress parametersVeterinary medicineSF600-1100ENVeterinary Sciences, Vol 8, Iss 274, p 274 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Keap1 metabolic syndrome NAFLD Nrf2 orlistat oxidative stress parameters Veterinary medicine SF600-1100
spellingShingle	Keap1 metabolic syndrome NAFLD Nrf2 orlistat oxidative stress parameters Veterinary medicine SF600-1100 Zaida Zakaria Zaidatul Akmal Othman Joseph Bagi Suleiman Nur Asyilla Che Jalil Wan Syaheedah Wan Ghazali Mahaneem Mohamed Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation
description	Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress parameters in high-fat diet (HFD) induced-MAFLD rats. Twenty-four male <i>Sprague-Dawley</i> rats were randomly divided into four groups (<i>n</i> = 6/group), i.e., Normal control (N), HFD, HFD + orlistat (HFD + O) (10 mg/kg/day administered concomitantly for 12 weeks as a protective model), and obese+orlistat (OB + O) (10 mg/kg/day administered 6 weeks after induction of obesity as a therapeutic model) groups. After 12 weeks, the HFD group had significantly increased Lee obesity index, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein levels, liver total cholesterol and triglyceride levels, insulin resistance and non-alcoholic steatohepatitis (NASH) together with decreased serum high-density lipoprotein level. Additionally, the HFD group also showed increased Nrf2 translocation to the nucleus with high Keap1 expression and increased liver oxidative stress parameters. Orlistat significantly improved all these alterations in HFD rats. We demonstrated that orlistat might have protective and therapeutic effects against HFD-induced MAFLD rats by its activation on Nrf2 signaling pathway, which subsequently improved metabolic syndrome and oxidative stress parameters.
format	article
author	Zaida Zakaria Zaidatul Akmal Othman Joseph Bagi Suleiman Nur Asyilla Che Jalil Wan Syaheedah Wan Ghazali Mahaneem Mohamed
author_facet	Zaida Zakaria Zaidatul Akmal Othman Joseph Bagi Suleiman Nur Asyilla Che Jalil Wan Syaheedah Wan Ghazali Mahaneem Mohamed
author_sort	Zaida Zakaria
title	Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation
title_short	Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation
title_full	Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation
title_fullStr	Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation
title_full_unstemmed	Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation
title_sort	protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress in high-fat diet-induced metabolic dysfunction-associated fatty liver disease (mafld) in rats: role on nrf2 activation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1b09adb6c145429d9726a57c523c48b7
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Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation

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