Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways
Purpose: This current study investigated the effect of metformin treatment on hepatic oxidative stress and inflammation associated with nonalcoholic fatty liver disease (NADLD) in high fat diet (HFD) fed rats. Method: Wistar rats were fed with a HFD or laboratory chow diet for 8 weeks. Metformin was...
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Elsevier
2021
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oai:doaj.org-article:8bfbbc0c52874c489257fcead5e3db982021-11-18T04:50:29ZMetformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways2405-580810.1016/j.bbrep.2021.101168https://doaj.org/article/8bfbbc0c52874c489257fcead5e3db982021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405580821002624https://doaj.org/toc/2405-5808Purpose: This current study investigated the effect of metformin treatment on hepatic oxidative stress and inflammation associated with nonalcoholic fatty liver disease (NADLD) in high fat diet (HFD) fed rats. Method: Wistar rats were fed with a HFD or laboratory chow diet for 8 weeks. Metformin was administered orally at a dose of 200 mg/kg. Body weight, food and water intake were recorded on daily basis. Oral glucose tolerance test (OGTT), biochemical analysis and histological examinations were conducted on plasma and tissue samples. Antioxidant and anti-inflammatory mRNA expression was analyzed using reverse transcription polymeric chain reaction (RT-PCR). Results: Metformin treatment for 8 weeks prevented HFD-induced weight gain and decreased fat deposition in HFD fed rats. Biochemical analysis revealed that metformin treatment significantly attenuated nitro-oxidative stress markers malondialdehyde (MDA), advanced protein oxidation product (APOP), and excessive nitric oxide (NO) levels in the liver of HFD fed rats. Gene expression analysis demonestrated that metformin treatment was associated with an enhanced expression of antioxidant genes such as Nrf-2, HO-1, SOD and catalase in liver of HFD fed rats. Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--γ, C/EBP-α, SREBP1c, FAS, AMPK and GLUT-4. Consistent with the biochemical and gene expression data, the histopathological examination unveiled that metformin treatment attenuated inflammatory cells infiltration, steatosis, hepatocyte necrosis, collagen deposition, and fibrosis in the liver of HFD fed rats. Conclusion: In conclusion, this study suggests that metformin might be effective in the prevention and treatment of HFD-induced steatosis by reducing hepatic oxidative stress and inflammation in the liver.Tahmina YasminMd Mizanur RahmanFerdous KhanFariha KabirKamrun NaharShoumen LaskerMd Didarul IslamMohammad Maqsud HossainRaquibul HasanSohel RanaMd Ashraful AlamElsevierarticleInflammationLipid peroxidationMetforminNon-alcoholic fatty liver diseaseObesityBiology (General)QH301-705.5BiochemistryQD415-436ENBiochemistry and Biophysics Reports, Vol 28, Iss , Pp 101168- (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Inflammation Lipid peroxidation Metformin Non-alcoholic fatty liver disease Obesity Biology (General) QH301-705.5 Biochemistry QD415-436 |
| spellingShingle |
Inflammation Lipid peroxidation Metformin Non-alcoholic fatty liver disease Obesity Biology (General) QH301-705.5 Biochemistry QD415-436 Tahmina Yasmin Md Mizanur Rahman Ferdous Khan Fariha Kabir Kamrun Nahar Shoumen Lasker Md Didarul Islam Mohammad Maqsud Hossain Raquibul Hasan Sohel Rana Md Ashraful Alam Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways |
| description |
Purpose: This current study investigated the effect of metformin treatment on hepatic oxidative stress and inflammation associated with nonalcoholic fatty liver disease (NADLD) in high fat diet (HFD) fed rats. Method: Wistar rats were fed with a HFD or laboratory chow diet for 8 weeks. Metformin was administered orally at a dose of 200 mg/kg. Body weight, food and water intake were recorded on daily basis. Oral glucose tolerance test (OGTT), biochemical analysis and histological examinations were conducted on plasma and tissue samples. Antioxidant and anti-inflammatory mRNA expression was analyzed using reverse transcription polymeric chain reaction (RT-PCR). Results: Metformin treatment for 8 weeks prevented HFD-induced weight gain and decreased fat deposition in HFD fed rats. Biochemical analysis revealed that metformin treatment significantly attenuated nitro-oxidative stress markers malondialdehyde (MDA), advanced protein oxidation product (APOP), and excessive nitric oxide (NO) levels in the liver of HFD fed rats. Gene expression analysis demonestrated that metformin treatment was associated with an enhanced expression of antioxidant genes such as Nrf-2, HO-1, SOD and catalase in liver of HFD fed rats. Metformin treatment also found to modulate the expression of fat metabolizing and anti-inflammatory genes including PPAR--γ, C/EBP-α, SREBP1c, FAS, AMPK and GLUT-4. Consistent with the biochemical and gene expression data, the histopathological examination unveiled that metformin treatment attenuated inflammatory cells infiltration, steatosis, hepatocyte necrosis, collagen deposition, and fibrosis in the liver of HFD fed rats. Conclusion: In conclusion, this study suggests that metformin might be effective in the prevention and treatment of HFD-induced steatosis by reducing hepatic oxidative stress and inflammation in the liver. |
| format |
article |
| author |
Tahmina Yasmin Md Mizanur Rahman Ferdous Khan Fariha Kabir Kamrun Nahar Shoumen Lasker Md Didarul Islam Mohammad Maqsud Hossain Raquibul Hasan Sohel Rana Md Ashraful Alam |
| author_facet |
Tahmina Yasmin Md Mizanur Rahman Ferdous Khan Fariha Kabir Kamrun Nahar Shoumen Lasker Md Didarul Islam Mohammad Maqsud Hossain Raquibul Hasan Sohel Rana Md Ashraful Alam |
| author_sort |
Tahmina Yasmin |
| title |
Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways |
| title_short |
Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways |
| title_full |
Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways |
| title_fullStr |
Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways |
| title_full_unstemmed |
Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways |
| title_sort |
metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/8bfbbc0c52874c489257fcead5e3db98 |
| work_keys_str_mv |
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| _version_ |
1718424988267053056 |