Abstract
BackgroundTreatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats.MethodsMale ZDF rats and Zucker lean rats aged 4–8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed.ResultsData demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats.ConclusionsThese results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats.
Highlights
Treatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology
Fourteen male Zucker diabetic fatty (ZDF) rats and six Zucker lean rats aged 4–8 weeks were divided into three groups: (1) ZDF rats treated with metformin (50 mg/kg body weight, n = 7), (2) ZDF rats treated with vehicle of distilled water (10 mL/kg, n = 7), and (3) Zucker lean rats treated with vehicle of distilled water (10 mL/kg, n = 6)
The weight gain in ZDF rats was not affected by the 6-month metformin treatment
Summary
The biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. We aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats. A biguanide that improves hepatic insulin resistance and hyperglycemia, is the first-line therapeutic agent for patients with type 2 diabetes, especially those who have hyperlipidemia and obesity [1, 2]. Sui et al Diabetol Metab Syndr (2019) 11:94 concentrations These adverse effects resolved after discontinuation of metformin treatment. The primary purpose of present study was to test the efficacy of metformin on the prevention of fatty liver disease in Zucker diabetic fatty (ZDF) rats. Young ZDF rats were treated with metformin for 6 months, followed by mRNA liver tissue array to investigate the long-term effects of metformin treatment on the development of hyperlipidemia and fatty liver disease
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