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

Abstract

Background Non-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. Methods Human 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. Results The 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. Conclusion This 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.

Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application

“…Polygonati Rhizoma and Polygonatum kingianum promote mitochondrial boxidation via increasing the CPT-1 activity to block long-chain fatty acid enter mitochondria, and improve mitochondrial function via inhibiting HFD-induced excessive production of ROS and malondialdehyde (MDA) . Nobiletin (Qi et al, 2018) and diosgenin (Fang et al, 2019) could lead to the reduction of ROS level and restoration of mitochondrial membrane potential. This mitochondrial interference suppressed lipid peroxidation that involved the increase of vital scavenger levels of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD).…”

Penthorum Chinense Pursh Protects Liver From Alcohol-induced Steatosis in Zebrafish by Mechanisms Including Inhibition of Oxidative Stress and Increase in Autophagy

“…MDA level was decreased and increased SOD, GSH and CAT level in our study. Moreover, P2 × 7R activation induces ROS production and antioxidative defense system imbalances [28], which is key factors in oxidative stress-driven cell fate [29], and the downstream AMPK prevents oxidative stress primarily by regulating glucose and lipid metabolism [30], which activates Nrf2. Nrf2 is the key to cellular resistance to ROS, and studies suggest that targeting Keap1/Nrf2 can effectively reduce oxidative stress [31], and related studies have also found that AMPK mediates oxidative stress by increasing intracellular levels of its co-substrate, NAD + , and that hyperphosphorylation of AMPK inhibits Nrf2 activation and nuclear translocation by modifying cysteine residues in Keap1, which in turn inhibits oxidative stress by inducing the expression of various antioxidant genes, such as HO-1 [32].…”

Gomisin N from Schisandra chinensis Ameliorates Lipid Accumulation and Induces a Brown Fat-Like Phenotype through AMP-Activated Protein Kinase in 3T3-L1 Adipocytes

“…ACC catalyzes production of malonyl-CoA, inhibiting lipogenesis and CTP1 expression. The phosphorylation of ACC by AMPK activation results in inactivation of ACC, so therefore CPT1 expression can be recovered and FAO promoted [33]. On the other hand, CC decreased p-AMPK and p-ACC, which was partially recovered by GN co-treatment ( Figure 4C,D).…”