Korean J Physiol Pharmacol.  2020 Jan;24(1):19-26. 10.4196/kjpp.2020.24.1.19.

Medium- and long-chain triglyceride propofol reduces the activity of acetyl-coenzyme A carboxylase in hepatic lipid metabolism in HepG2 and Huh7 cells

• Wang LY
• Wu J
• Gao YF
• Lin DM
• Ma J

• KMID: 2466566
• DOI: http://doi.org/10.4196/kjpp.2020.24.1.19

Abstract

Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 µg/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 µg/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 µg/ml MCT/LCT propofol for the subsequent experiments. Four and 8 µg/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.

Keyword

Hepatocytes; Liver; Metabolism; Propofol

MeSH Terms

Acetyl-CoA Carboxylase
AMP-Activated Protein Kinases
Cell Survival
Fatty Acids, Nonesterified
Hepatocytes
Intensive Care Units
Lipid Metabolism*
Liver
Metabolism
Phosphorylation
Propofol*
Triglycerides*
AMP-Activated Protein Kinases
Acetyl-CoA Carboxylase
Fatty Acids, Nonesterified
Propofol

Figure

• 

  Fig. 1 Cytotoxicity of free fatty acid (FFA) and medium- and long-chain triglyceride (MCT/LCT) propofol on hepatocytes. (A) HepG2 and Huh7 cells were treated with different concentrations of FFA, MTT was used to evaluate the cell viability. (B) HepG2 and Huh7 cells were treated with different concentrations of MCT/LCT propofol, then evaluated the cell viability. *p < 0.05 , **p < 0.01, ***p < 0.001 vs. control group.

• 

  Fig. 2 Medium- and long-chain triglyceride (MCT/LCT) propofol inhibited free fatty acid (FFA)-induced lipid accumulation in HepG2 and Huh7 cells. (A) After FFA and 4 µg/ml or 8 µg/ml MCT/LCT propofol treatment, Oil Red O staining was used to detect the accumulation of hepatic lipids. Relative intracellular lipid level was determined in HepG2 and Huh7 cells (Oil Red O staining, magnification, ×400). (B) After 4 µg/ml or 8 µg/ml MCT/LCT propofol treatment, the TG content in different groups were detected. *p < 0.05 vs. control group, #p < 0.05 vs. FFA group.

• 

  Fig. 3 Medium- and long-chain triglyceride propofol inhibited acetyl coenzyme A carboxylase (ACC)1 activity in HepG2 and Huh7 cells. (A) The ACC1 activity in HepG2 cell was detected by ELISA assay. (B) The ACC1 activity in Huh7 cell was measured. *p < 0.05 vs. 0 h group.

• 

  Fig. 4 Medium- and long-chain triglyceride propofol promoted the phosphorylation of acetyl coenzyme A carboxylase (ACC) in HepG2 and Huh7 cells. (A) Western blot was carried out to detect the expression and phosphorylation of ACC in different time points and concentrations in HepG2 and Huh7 cells. Pro (µg/ml) indicates Propofol (µg/ml). (B) Relative quantitative data analyses of p-ACC expression in HepG2 and Huh7 cells. *p < 0.05 vs. 0 h group.

• 

  Fig. 5 Medium- and long-chain triglyceride (MCT/LCT) propofol reversed free fatty acid (FFA)-induced phosphorylation inhibition of acetyl coenzyme A carboxylase (ACC) and AMPK in HepG2 and Huh7 cells. (A) Western blot was carried out to detect the expression and phosphorylation of ACC and AMPK after 4 µg/ml or 8 µg/ml MCT/LCT propofol treatment in HepG2 and Huh7 cells. (B) Relative quantitative data analyses of p-AMPK and p-ACC expression in HepG2 and Huh7 cells in different groups. *p < 0.05 vs. control group, #p < 0.05 vs. FFA group.

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