1. Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways
- Author
-
Ferdous Khan, Mohammad Maqsud Hossain, Didarul Islam, Shoumen Lasker, Ashraful Alam, Mizanur Rahman, Tahmina Yasmin, Raquibul Hasan, Sohel Rana, Fariha Kabir, and Kamrun Nahar
- Subjects
AST, aspartate aminotransferase ,Protein oxidation ,medicine.disease_cause ,Biochemistry ,LDL, low density lipoprotein ,SOD, Superoxide dismutase ,Lipid peroxidation ,AUC, area under the curve ,chemistry.chemical_compound ,TBARS, Thiobarbituric acid reactive substances ,Nonalcoholic fatty liver disease ,OGTT, Oral glucose tolerance test ,Biology (General) ,IL-6, interleukin-6 ,digestive, oral, and skin physiology ,Fatty liver ,PBS, Phosphate buffer saline ,SREBP1c, sterol regulatory element-binding protein 1c ,Malondialdehyde ,Metformin ,PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1 ,ATP, Adinosine triphosphate ,Research Article ,medicine.drug ,medicine.medical_specialty ,QH301-705.5 ,HSCs, Hepatic stellate cells ,MPO, Myeloperoxidase ,Biophysics ,QD415-436 ,IACUC, Institutional Animal Care and Use Committee ,ROS, reactive oxygen species ,ALT, alanine aminotransferase ,Internal medicine ,medicine ,FAS, Fatty acid synthase ,Obesity ,MDA, Malondialdehyde ,PPAR-γ, peroxisome proliferator-activated receptor γ ,Inflammation ,APOP, advanced protein oxidation product ,NO, nitric oxide ,ALP, alkaline phosphatase ,business.industry ,TBA, Thiobarbituric acid ,nutritional and metabolic diseases ,medicine.disease ,HDL, high density lipoprotein ,Met, Metformin ,AMPK, AMP-activated protein kinase ,Endocrinology ,chemistry ,HF, High fat ,NAFLD, nonalcoholic fatty liver disease ,CAT, catalase ,Steatosis ,business ,Oxidative stress ,Non-alcoholic fatty liver disease - Abstract
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., Highlights • High fat diet in rats developed glucose intolerance and oxidative stress in liver. • Metformin restored antioxidant genes expression in liver of HFD fed rats. • Metformin also inhibited the inflammatory genes expression and fibrosis in liver. • Moreover, metformin treatment may ameliorate fatty liver in HFD fed rats.
- Published
- 2021
- Full Text
- View/download PDF