Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation

Detalhes bibliográficos
Autor(a) principal: Sena, Cristina M.
Data de Publicação: 2018
Outros Autores: Cipriano, Maria Augusta, Botelho, Maria Filomena, Seiça, Raquel Maria
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/107691
https://doi.org/10.3390/ijms19092706
Resumo: Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.
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spelling Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activationdiabetessteatosisoxidative stressα-lipoic acidTNF-αNrf2 levelsAnimalsAntioxidantsDiabetes Mellitus, Type 2Diet, High-FatFatty LiverLipid PeroxidationMaleNF-E2-Related Factor 2Oxidative StressRatsRats, WistarThioctic AcidPrevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.MDPI2018-09-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107691http://hdl.handle.net/10316/107691https://doi.org/10.3390/ijms19092706eng1422-0067Sena, Cristina M.Cipriano, Maria AugustaBotelho, Maria FilomenaSeiça, Raquel Mariainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-27T09:43:53Zoai:estudogeral.uc.pt:10316/107691Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:00.778779Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
title Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
spellingShingle Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
Sena, Cristina M.
diabetes
steatosis
oxidative stress
α-lipoic acid
TNF-α
Nrf2 levels
Animals
Antioxidants
Diabetes Mellitus, Type 2
Diet, High-Fat
Fatty Liver
Lipid Peroxidation
Male
NF-E2-Related Factor 2
Oxidative Stress
Rats
Rats, Wistar
Thioctic Acid
title_short Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
title_full Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
title_fullStr Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
title_full_unstemmed Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
title_sort Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation
author Sena, Cristina M.
author_facet Sena, Cristina M.
Cipriano, Maria Augusta
Botelho, Maria Filomena
Seiça, Raquel Maria
author_role author
author2 Cipriano, Maria Augusta
Botelho, Maria Filomena
Seiça, Raquel Maria
author2_role author
author
author
dc.contributor.author.fl_str_mv Sena, Cristina M.
Cipriano, Maria Augusta
Botelho, Maria Filomena
Seiça, Raquel Maria
dc.subject.por.fl_str_mv diabetes
steatosis
oxidative stress
α-lipoic acid
TNF-α
Nrf2 levels
Animals
Antioxidants
Diabetes Mellitus, Type 2
Diet, High-Fat
Fatty Liver
Lipid Peroxidation
Male
NF-E2-Related Factor 2
Oxidative Stress
Rats
Rats, Wistar
Thioctic Acid
topic diabetes
steatosis
oxidative stress
α-lipoic acid
TNF-α
Nrf2 levels
Animals
Antioxidants
Diabetes Mellitus, Type 2
Diet, High-Fat
Fatty Liver
Lipid Peroxidation
Male
NF-E2-Related Factor 2
Oxidative Stress
Rats
Rats, Wistar
Thioctic Acid
description Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.
publishDate 2018
dc.date.none.fl_str_mv 2018-09-11
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/107691
http://hdl.handle.net/10316/107691
https://doi.org/10.3390/ijms19092706
url http://hdl.handle.net/10316/107691
https://doi.org/10.3390/ijms19092706
dc.language.iso.fl_str_mv eng
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dc.relation.none.fl_str_mv 1422-0067
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