Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells

Ke Fang,Guang Chen,Jingbin Li,Fuer Lu,Yan Zhao,Hui Dong,Xin Zou,Fan Wu,Lijun Xu

doi:10.1186/s12906-019-2671-9

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is characterized by excessive hepatic lipid accumulation. Many studies have suggested that lipid overload is the key initial factor that contributes to hepatic steatosis. Our previous study indicated that diosgenin (DSG) has a beneficial effect on energy metabolism, but the underlying mechanism remains unclear.MethodsHuman normal hepatocytes (LO2 cells) were incubated with palmitic acid to establish the cell model of nonalcoholic fatty liver. The effects of DSG on lipid metabolism, glucose uptake and mitochondrial function were evaluated. Furthermore, the mechanism of DSG on oxidative stress, lipid consumption and lipid synthesis in LO2 cells was investigated.ResultsThe results indicated that palmitic acid induced obvious lipid accumulation in LO2 cells and that DSG treatment significantly reduced the intracellular lipid content. DSG treatment upregulated expression of lipolysis proteins, including phospho-AMP activated protein kinase (p-AMPK), phospho-acetyl-coA carboxylase (p-ACC) and carnitine acyl transferase 1A (CPT-1A), and inhibited expression of lipid synthesis-related proteins, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Additionally, DSG-treated cells displayed a marked improvement in mitochondrial function, with less production of reactive oxygen species and a higher mitochondrial membrane potential compared with the model group.ConclusionThis study suggests that DSG can reduce intracellular lipid accumulation in LO2 cells and that the underlying mechanism may be related to the improving oxidative stress, increasing fatty acid β-oxidation and decreasing lipid synthesis. The above changes might be mediated by the activation of the AMPK/ACC/CPT-1A pathway and inhibition of the SREBP-1c/FAS pathway.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is characterized by excessive hepatic lipid accumulation
The effect of DSG on palmitic acid (PA)-induced cell injury Accompanied with lipid accumulation, PA supplementation increased the release of intracellular hepatic enzymes, such as ALT, AST and γ-GT (P < 0.01 vs control group) (Fig. 4a-c)
The effect of DSG on the AMP activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)/carnitine palmitoyl transferase (CPT)-1A and SREBP1c/fatty acid synthase (FAS) signaling pathway In order to explore the mechanism of DSG on ameliorating lipid accumulation in LO2 cells, we examined the protein expression of phospho-AMP activated protein kinase (p-AMPK), AMPK, phospho-acetyl-coA carboxylase (p-ACC), ACC, Carnitine acyl transferase 1A (CPT1A), SREBP-1c, FAS and β-actin

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is characterized by excessive hepatic lipid accumulation. NAFLD is characterized by excessive hepatic lipid accumulation and metabolic dysfunction. Many studies focused on activating liver FAO have suggested a potential approach to treat metabolic disorders, such as NAFLD and diabetes [4, 7, 8]. Accumulating evidence suggests that improving mitochondrial dysfunction is an effective strategy for reducing lipid overload. De novo lipogenesis in the liver greatly contributes to hepatic steatosis, and inhibition of fatty acid synthesis has been proven to be beneficial for NAFLD mice [3]. Evidence indicates that promoting FAO and inhibiting fatty acid synthesis under the condition of hepatic lipid accumulation are of substantial interest

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Discussion

Conclusion