Abstract
BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide. Metformin decreases triglyceride (TG) accumulation in hepatocytes in vivo and in vitro. Stearyl-coenzyme A desaturase 1 (SCD1) knockout mice also show decreased liver TG accumulation; however, whether SCD1 plays a role in the effect of metformin on TG accumulation is unknown. Therefore, the aim of this study was to investigate whether SCD1 mediated the effect of metformin on TG accumulation.MethodsHepG2 and AML12 cells were exposed to high glucose and high insulin with or without metformin. An adenovirus was used for the SCD1 knockdown and overexpression. The triglyceride level in cells was detected. The expression of related genes was detected by Western blot and quantitative real-time PCR. A dual-luciferase reporter assay was used to determine the effect of metformin on the transcriptional activity of the SCD1 promoter.ResultsMetformin decreased TG accumulation to normal level in HepG2 cells exposed to high glucose and high insulin. The expression of SCD1 and fatty acid synthetase (FAS) was also decreased to normal level by metformin. Knockdown of SCD1 mimicked the effect of metformin on decreasing TG levels in AML12 cells, and the overexpression of SCD1 attenuated the effect of metformin on decreasing TG accumulation in HepG2 cells. The dual-luciferase reporter assay showed that the transcriptional activity of the SCD1 promoter (− 550/+ 199) after metformin treatment was 2-fold lower compared to control group in HepG2 cells. Additionally, the phosphorylation of AMPK after metformin treatment was 2-fold higher, and the expression of sterol regulatory element-binding protein-1c (SREBP-1c) after metformin treatment was about 2-fold lower compared to high glucose and high insulin group in HepG2 cells.ConclusionsTogether, these results reveal that metformin reduces TG accumulation in HepG2 cells via inhibiting the expression of SCD1.
Highlights
The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide
We investigated whether adenosine monophosphate-activated protein kinase (AMPK)-sterol regulatory element-binding protein-1c (SREBP-1c) pathway was associated with the effect of metformin on reducing Stearyl-coenzyme A desaturase 1 (SCD1) expression
Metformin decreases TG accumulation in HepG2 cells exposed to high glucose and high insulin We investigated whether metformin could decrease TG accumulation in HepG2 cells
Summary
The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide. Metformin decreases triglyceride (TG) accumulation in hepatocytes in vivo and in vitro. Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive triglyceride (TG) accumulation in hepatocytes after excluding overt alcohol consumption and other liver injury factors, the spectrum of which ranges from steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis and even to hepatocellular carcinoma (HCC) [1]. The global prevalence of NAFLD is approximately 25.24% at present [2]. The prevalence of NAFLD in China is increasing rapidly, ranging from 6. A study showed that the prevalence of NAFLD in patients with type 2 diabetes (T2DM) and normal aminotransferase levels reached 36%, which is much higher than that of the general population [4]. There is no effective drug available for NAFLD at present
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